10-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

For the fiscal year ended December 31, 2024

Commission File Number 001-41374

PEPGEN INC.

(Exact name of Registrant as specified in its Charter)

(Address of principal executive offices) (Zip Code)

Registrant’s telephone number, including area code: (781) 797-0979

Securities registered pursuant to Section 12(b) of the Act:

Title of each class TradingSymbol(s) Name of each exchange on which registered

Common stock, par value $0.0001 per share PEPG Nasdaq Global Select Market

Securities registered pursuant to Section 12(g) of the Act: None

Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒

Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). Yes ☒ No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

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. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐

Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

The aggregate market value of the voting and non-voting common equity held by non-affiliates of the Registrant, based on the closing price of the shares of common stock on Nasdaq Global Select Market on June 30, 2024, was $272.9 million. The number of shares of Registrant’s Common Stock outstanding as of February 18, 2025 was 32,692,388.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s Definitive Proxy Statement relating to its 2025 Annual Meeting of Stockholders to be filed hereafter are incorporated by reference into Part III of this Annual Report on Form 10-K where indicated.

Auditor Firm Id: 185 Auditor Name: KPMG LLP Auditor Location: Phoenix, AZ, USA

Table of Contents

Page

PART I

Item 1. Business 4

Item 1A. Risk Factors 38

Item 1B. Unresolved Staff Comments 98

Item 1C. Cybersecurity 98

Item 2. Properties 98

Item 3. Legal Proceedings 98

Item 4. Mine Safety Disclosures 99

PART II

Item 6. [Reserved] 100

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 109

Item 8. Financial Statements and Supplementary Data 109

Item 9A. Controls and Procedures 109

Item 9B. Other Information 110

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 110

PART III

Item 10. Directors, Executive Officers and Corporate Governance 111

Item 11. Executive Compensation 111

Item 14. Principal Accounting Fees and Services 111

PART IV

Item 15. Exhibits, Financial Statement Schedules 112

SPECIAL NOTE REGARDING FORWARD LOOKING STATEMENTS

This Annual Report on Form 10-K, or 10-K, contains express or implied forward-looking statements that are based on our management’s belief and assumptions and on information currently available to our management and which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act. Although we believe that the expectations reflected in these forward-looking statements are reasonable, these statements relate to future events or our future operational or financial performance, and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Forward-looking statements in this 10-K include, but are not limited to, statements about:

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the initiation, timing, progress, results, and cost of our research and development programs and our current and future preclinical studies and clinical trials, including statements regarding the timing of initiation and completion of studies or trials and related preparatory work, and the period during which the results of our clinical trials will become available;

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our ability to efficiently develop our existing product candidates and discover new product candidates;

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our ability to successfully manufacture our investigational drug substances and drug product for preclinical use, for clinical trials and on a larger scale for commercial use, if our investigational drug candidates are approved;

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our ability to obtain funding for our operations necessary to complete further development and commercialization of our product candidates;

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our ability to obtain and maintain regulatory approval of our product candidates;

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our ability to commercialize our product candidates, if approved;

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the pricing and reimbursement of our product candidates, if approved;

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the implementation of our business model, and strategic plans for our business and product candidates;

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the scope of protection we are able to establish and maintain for intellectual property rights covering our product candidates and our technology platform;

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estimates of our future expenses, revenues, capital requirements, and our needs for additional financing;

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the size and growth potential of the markets for our product candidates, and our ability to serve those markets;

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our financial performance;

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the rate and degree of market acceptance of our product candidates;

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regulatory developments in the United States, or U.S., and foreign countries;

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our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately, and our ability to identify and contract with alternative third-party suppliers and manufacturers in a timely manner and on reasonable terms, if needed;

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our ability to produce our products or product candidates with advantages in turnaround times or manufacturing cost;

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the success of competing therapies that are or may become available;

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our ability to attract and retain key research and development or management personnel;

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the impact of laws and regulations;

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developments relating to our competitors and our industry;

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the effects of any epidemics or pandemics, including mitigation efforts and economic effects, on any of the foregoing or other aspects of our business operations, including but not limited to our preclinical studies and clinical trials and any future studies or trials; and

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other risks and uncertainties, including those listed under the caption “Risk Factors.”

In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “intends,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “continue” or the negative of these terms or other

comparable terminology. These statements are only predictions, and are subject to change due to known and unknown risks, uncertainties, and other factors, which are, in some cases, beyond our control and which could materially affect results. Factors that may cause actual results to differ materially from current expectations include, among other things, those listed under the section titled “Risk Factors” and elsewhere in this 10-K. If one or more of these risks or uncertainties occur, or if our underlying assumptions prove to be incorrect, actual events or results may vary significantly from those implied or projected by the forward-looking statements. No forward-looking statement is a guarantee of future performance. Moreover, we operate in an evolving environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties. You should read this 10-K and the documents that we reference in this 10-K and have filed with the U.S. Securities and Exchange Commission, or the SEC, completely and with the understanding that our actual future results may be materially different from any future results expressed or implied by these forward-looking statements.

The forward-looking statements in this 10-K represent our views as of the date of this 10-K. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we have no current intention of doing so except to the extent required by applicable law. You should therefore not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this 10-K.

In addition, statements that "we believe" and similar statements reflect our beliefs and opinions on the relevant subject. These statements are based upon information available to us as of the date of this 10-K, and while we believe such information forms a reasonable basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain.

This 10-K also contains estimates, projections and other information concerning our industry, our business and the markets for our programs and product candidates. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances that are assumed in this information. Unless otherwise expressly stated, we obtained this industry, business, market, and other data from our own internal estimates and research as well as from reports, research surveys, studies, and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data and similar sources. While we are not aware of any misstatements regarding any third-party information presented in this 10-K, their estimates, in particular, as they relate to projections, involve numerous assumptions, are subject to risks and uncertainties and are subject to change based on various factors, including those discussed under the section titled “Risk Factors” and elsewhere in this 10-K.

TRADEMARKS

This 10-K contains references to our trademarks and to trademarks belonging to other entities. Solely for convenience, trademarks and trade names referred to, including logos, artwork and other visual displays, may appear without the ® or TM symbols, but such references are not intended to indicate, in any way, that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. We do not intend our use or display of other companies’ trade names or trademarks to imply a relationship with, or endorsement or sponsorship of us by, any other companies.

SUMMARY OF RISK FACTORS

Our business is subject to numerous risks and uncertainties that you should be aware of in evaluating our business. These risks include, but are not limited to, the following:

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We have incurred significant losses since our inception, have no products approved for sale and we expect to incur losses for the foreseeable future.

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We will need to raise substantial additional funding. If we are unable to raise capital when needed, we could be forced to delay, scale back, or discontinue our product development programs or future commercialization efforts.

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We are early in our development efforts. We have only completed a Phase 1 clinical trial and initiated Phase 2 clinical trials for our first product candidate, as well as initiated an additional Phase 1 clinical trial and more recently, a Phase 2 clinical trial of a second product candidate, and as a result it will be years before we commercialize a product candidate, if ever. If we are unable to advance our product candidates through preclinical studies and clinical trials, obtain marketing approval and ultimately commercialize them, or experience significant delays in doing so, our business will be materially harmed.

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Our business is highly dependent on the clinical advancement of our programs and modalities and is especially dependent on the success of our lead product candidates, PGN-EDO51 and PGN-EDODM1. Delay or failure to advance programs or modalities, including PGN-EDO51 and PGN-EDODM1, including as a result of a clinical hold or other regulatory action, could adversely impact our business.

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Preclinical and clinical development involves a lengthy and expensive process with an uncertain outcome, and the results of preclinical and clinical studies, including studies of PGN-EDO51, PGN-EDODM1 and other research candidates, are not necessarily predictive of the results of later preclinical studies and any clinical trials of our product candidates. Our product candidates may not have favorable results in clinical trials, if any, or receive regulatory approval on a timely basis, if at all.

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Substantial delays in the commencement, enrollment or completion of our clinical trials and advancement of our clinical trials, including as a result of clinical hold or other regulatory action, or failure to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities could prevent us from commercializing product candidates we determine to develop on a timely basis, if at all.

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We rely, and expect to continue to rely, on third parties to conduct some or all aspects of our product manufacturing, research, preclinical and clinical testing, and these third parties may not perform satisfactorily. If we have to replace one or more of these third parties, we may be unable to enter into new agreements in a timely manner or on reasonable terms, if at all.

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We face significant competition, and if our competitors develop technologies or product candidates more rapidly than we do or their technologies or product candidates are more effective or have more favorable safety or tolerability profiles, our business and our ability to develop and successfully commercialize products may be adversely affected.

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If we are unable to obtain and maintain patent protection for our Enhanced Delivery Oligonucleotide platform, therapeutic development candidates or programs and/or other proprietary technologies we develop, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize products and technology similar or identical to ours, and our ability to successfully commercialize our therapeutic product candidates or programs and other proprietary technologies we may develop may be adversely affected.

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We expect to expand our headcount to support our development and regulatory capabilities and potentially implement sales, marketing and distribution capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.

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Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.

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The price of our common stock is volatile and fluctuates substantially, which could result in substantial losses for holders of our common stock.

The summary risk factors described above should be read together with the text of the full risk factors below in the section titled “Risk Factors” in Part I, Item 1.A. and the other information set forth in this 10-K, as well as in other documents that we file with the SEC. The risks summarized above or described in full below are not the only risks that we face. Additional risks and uncertainties not precisely known to us, or that we currently deem to be immaterial, may also materially adversely affect our business, financial condition, results of operations and future growth prospects.

PART I

Item 1. Business.

Overview

PepGen Inc. (also referred to as “PepGen,” “we,” “our” or “us”) is a clinical-stage biotechnology company advancing the next generation of oligonucleotide therapeutics with the goal of transforming the treatment of severe neuromuscular and neurologic diseases. Our proprietary Enhanced Delivery Oligonucleotide, or EDO, platform is founded on over a decade of research and development and leverages cell-penetrating peptides, or CPPs, to improve the uptake and activity of conjugated oligonucleotide therapeutics. Our EDO peptides are engineered to optimize tissue penetration, cellular uptake and nuclear delivery, and in preclinical studies we have observed their ability to transport oligonucleotides into a broad range of target tissues, including smooth, skeletal, and cardiac muscle. We have also demonstrated robust delivery and activity of oligonucleotides to skeletal muscle in our early clinical trials with our investigational therapeutics, PGN-EDO51 and PGN-EDODM1. Furthermore, the high levels of pharmacological activity observed in preclinical and clinical studies support our belief that our EDO platform technology has the potential to deliver therapeutic agents to the nucleus of the target cells. Using these EDO peptides, we are generating a pipeline of oligonucleotide product candidates that target the root cause of serious diseases.

We are initially focused on addressing the underlying cause of Duchenne muscular dystrophy, or DMD, and myotonic dystrophy type 1, or DM1, that have high unmet need. Our current pipeline depicted below consists of two clinical stage programs - PGN-EDO51 for DMD patients who are amenable to exon 51 skipping and PGN-EDODM1 for DM1 patients, as well as a number of additional preclinical stage programs. We anticipate expanding this pipeline over time to include other neuromuscular targets as well as potential opportunities in neurologic diseases.

PGN-EDO51

We are developing PGN-EDO51 to treat DMD patients whose mutations are amenable to an exon 51-skipping approach. We completed a first-in-human Phase 1 clinical trial in healthy volunteers, or HVs, with PGN-EDO51 in the third quarter of 2022. Our ongoing clinical development program for PGN-EDO51 is comprised of two parallel Phase 2 studies of PGN-EDO51 in DMD patients. The first study, CONNECT1-EDO51, or CONNECT1, is an ongoing open-label, multiple ascending dose, or MAD, study in boys and young men living with DMD being conducted in Canada. The CONNECT1 study was designed to provide proof-of-concept for our EDO platform and PGN-EDO51, as well as inform the design and conduct of our CONNECT2-EDO51, or CONNECT2, study. We reported initial clinical data from CONNECT1 in the third quarter of 2024 from the 5 mg/kg dose cohort which we believe demonstrate a favorable emerging safety profile and promising early exon skipping and dystrophin production levels. The 10 mg/kg cohort is fully enrolled and participants in the 5 mg/kg cohort are continuing to dose at that level in the long-term extension, or LTE, phase of the study. We expect to report clinical data from the 10 mg/kg cohort by the end of the third quarter of 2025. We have received communication from Health Canada that dosing of participants in the 5 and 10 mg/kg cohorts may continue at their current dose levels. Health Canada has requested additional information from us to address its safety concerns before any further dose escalation or enrollment of any additional participants at the current dose levels. We are working with Health Canada to address its questions.

The second study, CONNECT2, is a randomized, double-blind, placebo-controlled MAD study. The CONNECT2 study is open in the U.K., with plans to evaluate opening the study in other geographies subject to regulatory authorizations. In December 2024, we announced that we received a clinical hold notice from the U.S. Food and Drug Administration, or FDA, regarding our investigational new drug, or IND, application to initiate the CONNECT2 study in the U.S. We are working with the FDA to address its questions regarding supportive data for the dosing levels planned for the patient population.

The CONNECT2 study has been designed and optimized based on learnings from the CONNECT1 study and, together with data from the CONNECT1 study, is intended to support a potential accelerated approval pathway for PGN-EDO51, subject to regulatory authority feedback. Based on the high levels of exon skipping observed in both the Phase 1 trial in HVs and the early results from the CONNECT1 trial at 5 mg/kg in DMD patients, we believe that higher doses and a longer duration of treatment with PGN-EDO51 may lead to therapeutically relevant accumulation of DMD exon 51-skipped transcript and an associated increase in dystrophin protein in patients, which may in turn drive meaningful clinical benefit for those who live with this devastating, progressive, life-shortening disease.

PGN-EDODM1

We are also developing PGN-EDODM1 for the treatment of DM1 and are utilizing what we believe to be a unique mechanism of action and a different delivery approach compared to other approaches in more advanced stages of clinical development. The therapeutic oligonucleotide component of PGN-EDODM1 is engineered to bind to the pathogenic cytosine-uracil-guanine, or CUG repeat expansion present in the myotonic dystrophy protein kinase, or DMPK, messenger RNA, or mRNA, of DM1 patients, thus reducing the ability of these expanded trinucleotide repeats to bind and sequester RNA binding proteins including MBNL1, a critical RNA splicing factor. The liberation of MBNL1 in turn leads to the correction of downstream mis-splicing events that drive the pathology of DM1. We believe this approach, which is not designed to knock down or degrade DMPK transcript, has the potential to selectively and directly address the underlying genetic defect central to this disease. In a DM1 mouse model, the HSALR mouse, following single and repeat dosing of PGN-EDODM1 every four weeks, we observed robust correction of mis-splicing and resolution of myotonia.

Our clinical development program for PGN-EDODM1 includes two ongoing studies. FREEDOM-DM1, or FREEDOM, is a Phase 1 multinational, randomized, double-blind, placebo-controlled, single ascending dose, or SAD, study, designed to assess PGN-EDODM1's safety and pharmacokinetics. In addition, the study will explore the potential impact of PGN-EDODM1 on splicing correction, and functional outcome measures in DM1 patients. On February 24, 2025, we reported initial data from the 5 mg/kg and 10 mg/kg dose cohorts in this study. PGN-EDODM1 was observed to have a favorable emerging safety profile and robust splicing correction in a dose-dependent manner in the 5 and 10 mg/kg dose cohorts. The 15 mg/kg cohort is currently enrolling participants and we have begun dosing at this level. We anticipate reporting data from this cohort in the second half of 2025. The second study, FREEDOM2-DM1, or FREEDOM2, is a Phase 2 multinational, randomized, double-blind, placebo-controlled MAD study in DM1 patients. We have received clearance from Health Canada and the Medicines and Healthcare products Regulatory Agency, or MHRA, to initiate FREEDOM2 in Canada and the U.K., respectively. This study is currently dosing participants in the 5 mg/kg dose cohort and we expect to report data from this cohort in the first quarter of 2026.

Additional Discovery and Preclinical Programs

In addition to these lead clinical stage programs, we are evaluating EDO candidates for additional DMD sub-populations amenable to skipping of other exons, including exon 53, 45 and 44. We have previously reported robust exon 53-skipping levels following either a single dose or multiple doses in non-human primates, or NHPs, for our PGN-EDO53 program. We have also initiated research efforts for additional indications, including neuromuscular diseases and neurologic disorders.

Our EDO Platform

Background on Oligonucleotide Therapeutics

Oligonucleotide therapeutics consist of small single or double stranded segments of deoxyribonucleic acid, or DNA, or ribonucleic acid, or RNA, molecules that are made up of nucleotides that bind to their targets via complementary Watson-Crick base pairing thereby modulating the expression of their target DNA or RNA sequence, thereby addressing the root cause of many diseases. Upon binding to their target sequence, oligonucleotides can modulate function through the modulation of RNA expression and processing. The mechanisms of action of these medicines include interference with gene expression; degradation of toxic RNA species; alteration of gene translation; interference with interactions between RNA and other nucleic acids or proteins; endogenous human adenosine deaminase acting on RNA, or ADAR; site-directed RNA editing; and modulation of the splicing of transcripts. Each of these approaches can lead to profound biological effects. The development of oligonucleotide therapeutics has enabled the targeting of a diverse set of diseases that have proven difficult to treat through other approaches due to their high degree of specificity to target pathogenic mutations.

Oligonucleotide therapeutics have demonstrated clinical benefit and been approved for the treatment of multiple diseases, such as spinal muscular atrophy, DMD, familial hypercholesterolemia and hereditary transthyretin-mediated amyloidosis. These approved drugs span two classes – ASOs, which are short, synthetic, single-stranded oligonucleotides, and small interfering RNAs, or siRNAs, which are double-stranded oligonucleotides. ASOs and siRNAs both bind their target mRNAs or pre-mRNAs but differ in their respective modes of action. ASOs are designed to either (i) degrade target RNA species through an RNAse-H-mediated process, or (ii) modulate RNA-RNA and/or RNA-protein interactions through a steric blocking mechanism. In contrast, siRNAs are designed to silence or knockdown a particular mRNA through the RNA interference, or RNAi, pathway.

ASOs are typically synthetic molecules that may contain modified nucleotide bases, sugars and phosphate linkages designed to overcome the historical limitations of unmodified oligonucleotides, including instability, immunogenicity and a poor pharmacological profile. Many approved oligonucleotides incorporate a modified oligonucleotide backbone in which the phosphate and ribose sugars are replaced by phosphorodiamidate morpholino groups, or PMOs. The resulting PMOs are resistant to multiple hydrolases in serum, while their uncharged nature ensures that they do not interact strongly with proteins in a nonspecific way. PMOs have shown

promising results in early-stage preclinical studies and have become marketed products for the treatment of a host of diseases. For example, EXONDYS 51® (eteplirsen), marketed by Sarepta Therapeutics, Inc., or Sarepta, is a PMO that was approved in 2016 for individuals with DMD who are amenable to exon 51 skipping but has left much room for improvement given its relatively low tissue and cell penetration and minimal induction of dystrophin production.

The Challenge of Oligonucleotide Delivery

In order for oligonucleotide therapeutics to exert their intended effect, they must first gain access to the nucleus where mRNAs are synthesized and processed. Historically, the delivery of oligonucleotides to the interior of the cell proved challenging due to their high molecular weight and the lack of a specific mechanism to facilitate their transport across the cell membrane and escape the endosome to enter the cytoplasm and nucleus. Several methods have been developed to increase the cellular uptake of oligonucleotides, the most clinically advanced of which is the covalent attachment of CPPs. CPPs are designed to facilitate the transport of oligonucleotides across the plasma membrane, thus allowing these cargo species to reach their eventual site of action in the nucleus. We believe that these capabilities are critical in enabling oligonucleotides to exert their intended therapeutic effect within the cell. Early research into CPPs showed that simple peptides consisting primarily of multiple arginine residues could increase the cellular uptake of oligonucleotides and increase their activity in modulating RNA splicing. However, a considerable number of these early CPPs were found to be highly toxic in animal models, and in many instances, there existed a direct correlation between toxicity and activity, which limited the clinical translation and development of these first-generation delivery vectors.

Our Approach: A Solution for the Oligonucleotide Delivery Challenge

Our EDO platform is based on novel CPP technology. We engineered our proprietary EDO technology to optimize cellular uptake and nuclear delivery, which we believe may enhance therapeutic activity and improve the tolerability of oligonucleotide therapeutics. This technology is founded on over a decade of research and development conducted in the academic laboratories of our founders Michael Gait, Ph.D. at the Medical Research Council Laboratory of Molecular Biology in Cambridge, United Kingdom, or MRC, and Professor Matthew Wood, M.D., Ph.D. at the University of Oxford, United Kingdom.

Our EDO platform peptides possess the following key structural characteristics:

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Two positively charged, arginine-rich regions, one at the N-terminus and the other at the C-terminus interspersed with non-natural amino acids to confer greater peptide stability;

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A central core rich in hydrophobic residues that separates the arginine-rich regions and is distinct from the older generation of CPPs, known as PIP peptides, and contributes to endosomal escape; and

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A linear peptide sequence with a length of less than 20 amino acids designed to be non-immunogenic.

Our EDO peptides were developed through an iterative optimization process that selected simultaneously for: biodistribution to muscle tissue; high cellular uptake; endosomal escape, where the therapeutic agent is released from the endosomes, a sub-cellular organelle, in a functional form and delivered to the cell nucleus; and acceptable tolerability. We utilize PMOs in our approach, and these therapeutic cargos are conjugated to one of our optimized, proprietary, novel EDO peptides to generate our lead EDO product candidates - peptide conjugated PMOs, or PPMOs. We intend to continue to build and develop this platform technology to enable us to expand into new therapeutic areas.

We believe that our therapeutic candidates may offer the following advantages with the goal of enabling the safe and efficient delivery of oligonucleotide cargos:

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Enhanced delivery to the nucleus of skeletal muscle. We have observed in preclinical and early clinical studies that our peptides demonstrated enhanced delivery of their cargo oligonucleotide therapeutics to the nucleus of skeletal muscle. We believe that EDO peptides have the potential to promote endosomal escape and facilitate the robust delivery of cargo oligonucleotides to the cell nucleus. We have now shown in in vitro and in NHP models, and more recently in early clinical studies, that our EDO technology can mediate higher uptake of oligonucleotide in the nucleus.

PGN-EDODM1 treatment results in higher nuclear delivery of PMO. 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.

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Encouraging activity and favorable emerging safety profile observed in a Phase 1 HV clinical study and in early data from Phase 2 clinical study of PGN-EDO51 and Phase 1 clinical study of PGN-EDODM1.

In our Phase 1 clinical study of PGN-EDO51 in HVs, we observed high levels of mean exon skipping in skeletal muscle following a single dose. Post hoc analyses showed high exon skipping levels that correlated with high uptake of PGN-EDO51 in the myocytes and nuclei.

HVs were dosed with placebo or 10 mg/kg of PGN-EDO51 via IV infusion.Representative image from one subject’s bicep samples collected at day 10 and assessed for PGN-EDO51 levels in post hoc in situ hybridization analysis using probe targeting the PMO sequence. Arrows denote nuclei positive for PMO.

In our Phase 2 CONNECT1 clinical study of PGN-EDO51 in DMD patients, we observed high levels of exon 51 skipping in skeletal muscle after three months and four doses at 5 mg/kg. We believe PGN-EDO51 has been observed to have a favorable emerging safety profile at 5 mg/kg and 10 mg/kg through January 23, 2025.

In our Phase 1 FREEDOM study of PGN-EDODM1 in DM1 patients, we observed robust splicing correction in skeletal muscle at the 5 and 10 mg/kg dose levels, which we believe further supports the platform potential of EDOs across multiple neuromuscular diseases.

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Robust, scalable and cost-efficient manufacturing that does not require cell-based processes. We have developed a modular manufacturing process that is highly scalable, easily characterizable, and utilizes readily available building blocks. This process is fully synthetic in nature and does not rely on microbial fermentation, thus substantially reducing the risk of introducing microbial DNA or protein into our product candidates.

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Efficient development of pipeline therapeutic candidates enabled by use of a single EDO peptide across all our initial programs. We currently utilize the same EDO delivery peptide across all of our programs. We intend to apply our knowledge and learnings from our current lead programs in order to efficiently pursue our future programs, and we will additionally aim to take advantage of economies of scale in our manufacturing processes.

Our Strategy

Our goal is to become a leading biopharmaceutical company focused on the development and commercialization of oligonucleotide therapies to transform the lives of patients with severe neuromuscular and neurologic diseases. We aim to accomplish this goal by implementing the following strategies:

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Advance PGN-EDODM1 through clinical trials and potential regulatory approval. We are developing PGN-EDODM1, an EDO peptide conjugated to a PMO therapeutic cargo to treat DM1 patients and have observed robust pharmacological activity in preclinical models with both long and short cytosine-thymine-guanine, or CTG repeats. In the FREEDOM Phase 1 clinical study of PGN-EDODM1 in DM1 patients, PGN-EDODM1 was observed to have a favorable emerging safety profile and robust splicing correction in a dose-dependent manner in the 5 and 10 mg/kg dose cohorts.

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Advance PGN-EDO51 through clinical trials and potential regulatory approval. We are developing PGN-EDO51, which utilizes the same EDO peptide as PGN-EDODM1 conjugated to a PMO therapeutic cargo to treat DMD patients whose mutations are amenable to an exon 51-skipping approach. There is no cure for DMD and approved exon-skipping therapies or advanced stage exon-skipping investigational candidates for patients who are amenable to exon 51 skipping are

thought to have limited impact on disease progression due to low levels (<5%) of unadjusted dystrophin production. In the CONNECT1 Phase 2 clinical study of PGN-EDO51 in DMD patients, the 5 mg/kg low dose of PGN-EDO51 was observed to have a favorable emerging safety profile and produced mean exon skipping of 2.15% at week 13 compared to baseline, measured by RT-PCR, and generated encouraging levels of dystrophin production.

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Leverage the full potential of our EDO technology to expand into treatment of additional DMD patient populations as well as new neuromuscular and neurological disease areas. Given the potential of the EDO technology to efficiently deliver nucleic acid payloads such as PMOs to skeletal muscle, cardiac tissue and diaphragm, we are looking to develop disease-modifying peptide-conjugated oligonucleotide candidates for the potential treatment of other neuromuscular and neurological indications, including other DMD populations.

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Utilize the modular nature of our EDO platform to evaluate new cargos and peptide technologies. We believe that our EDO technology has the potential to facilitate the delivery of multiple classes of nucleic acid payloads, including other oligonucleotide therapeutics, and longer-term, we intend to expand the scope of the cargos that can be delivered by our EDO platform as part of our ongoing platform development work.

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Maximize the value of our pipeline and our EDO platform by selectively exploring strategic collaborations. We have a disciplined strategy to maximize the value of our pipeline and currently have worldwide development and commercial rights to all of our product candidates. Given the potential of our EDO platform, we may opportunistically enter into strategic collaborations around certain geographies, targets or programs. We may seek to build such relationships where we believe the resources and expertise of a third-party pharmaceutical or biotechnology company could be beneficial to the development or commercialization of our product candidates or to the expansion of our platform capabilities.

Our Portfolio

We are harnessing the power of our EDO platform to generate a pipeline of oligonucleotide therapeutic candidates. Our EDO conjugates have been engineered to successfully target the root cause of serious diseases while maintaining a tolerability profile that is acceptable for clinical use. We are initially focused on addressing neuromuscular indications and are building a portfolio of therapeutic candidates to address the underlying genetic mutations found in DMD and DM1, with our current pipeline being comprised of multiple programs, two clinical and several preclinical.

In the future, we anticipate expanding this pipeline to include other neuromuscular targets, along with potential opportunities in neurologic indications, and we will seek to leverage the modular, scalable nature of our EDO technology to support our expansion into these new therapeutic areas. We have worldwide development and commercialization rights to all our programs.

PGN-EDO51

Overview

Our initial product candidate is PGN-EDO51, an EDO peptide conjugated to a PMO, that we are developing for the treatment of DMD patients with mutations amenable to an exon 51-skipping approach. An exon is a segment of a gene that, together with other exons, contains the genetic code that is translated into a protein. Exon skipping is a therapeutic mechanism that enables mutations in the gene to be bypassed, thereby repairing this code or reading frame and enabling production of a truncated, yet functional version of the target protein. PGN-EDO51 is designed to splice out exon 51 and potentially additional exons depending on the mutation of the dystrophin pre-mRNA, resulting in the restoration of the open reading frame of the dystrophin transcript and production of an internally deleted, yet functional dystrophin protein. We have completed a Phase 1 clinical trial of PGN-EDO51 in HVs, in which we observed high levels of exon skipping in humans following a single dose. In this Phase 1 clinical trial, PGN-EDO51 was observed to be generally well-tolerated at potentially clinically relevant dose levels.

We are currently advancing PGN-EDO51 in two Phase 2 studies, CONNECT1 and CONNECT2. In July 2024, we reported initial data from CONNECT1, an open-label MAD study in DMD patients amenable to an exon 51-skipping approach underway in Canada. PGN-EDO51 was observed to have a favorable emerging safety profile and encouraging exon skipping levels and dystrophin production at the starting dose of 5 mg/kg. We have fully enrolled the 10 mg/kg dose cohort and participants in the 5 mg/kg cohort are continuing to dose at that level in the LTE phase of the study. We expect to report initial safety, exon skipping and dystrophin production data from the 10 mg/kg cohort by the end of the third quarter of 2025. We have received communication from Health Canada that dosing of participants in the 5 and 10 mg/kg cohorts may continue at their current dose levels. Health Canada has requested additional information from us to address its safety concerns before any further dose escalation or enrollment of any additional participants at the current dose levels. We are working with Health Canada to address its questions. Our second Phase 2 study of PGN-EDO51, CONNECT2, is a randomized, placebo-controlled MAD study, which, together with data from the CONNECT1 study, is intended to support a potential accelerated approval pathway for PGN-EDO51, subject to regulatory authority feedback. The CONNECT2 study is open in the U.K., with plans to evaluate opening the study in other geographies subject to regulatory authorizations. In December 2024, we announced that we received a clinical hold notice from the FDA regarding our IND application to initiate the CONNECT2 study in the US. We are working with the FDA to address its questions regarding supportive data for the dosing levels planned for the patient population.

The FDA has granted both orphan drug designation and rare pediatric disease designation, or RPDD, for PGN-EDO51 for the treatment of DMD patients who are amenable to exon 51 skipping.

Disease Background and Prevalence

DMD is a debilitating X-linked recessive, progressive, muscle-wasting disease that predominantly affects boys. It is one of the most prevalent rare genetic diseases globally, with an incidence of up to 1 in 3,500 to 5,000 live male births, and it is invariably fatal by young adulthood. There are up to 15,000 DMD patients in the U.S., approximately 25,000 DMD patients in Europe and approximately 5,000 in Japan. DMD is caused by mutations in the gene encoding dystrophin, a protein necessary for normal muscle function. The primary role of dystrophin is as a shock absorber, and this protein allows muscle cells to retain their structural integrity while under mechanical stress. In the absence of dystrophin, muscle fibers are no longer protected from the mechanical forces of contraction, which leads to cell death, fibrotic tissue formation and muscle degeneration resulting in loss of ambulation.

Early symptoms of disease include difficulty walking or jumping, loss of balance, and increased fatigue when compared to healthy peers. By their mid-teenage years, most DMD patients will need to use a wheelchair on a regular basis. As the disease progresses, life-threatening heart and respiratory conditions become common. Dilated cardiomyopathy – a condition where the cardiac muscle becomes weakened and the chambers of the heart are enlarged – often arises, and heart failure is a leading cause of death in DMD patients. Pulmonary function also becomes progressively impaired as the dystrophic process affects respiratory muscles, including the diaphragm, leading to significant morbidity and mortality. DMD patients ultimately succumb to cardiac and respiratory failure in early adulthood, with a mean lifespan of approximately 25 years. Therefore, the restoration of dystrophin is a compelling therapeutic strategy, and a number of therapeutic modalities have been explored with this goal in mind. However, the nature of the DMD gene, the range of mutations implicated in DMD, and the large size of the dystrophin protein itself provide considerable obstacles to this approach.

The DMD gene, at 2.1 million base pairs and 79 exons, is one of the largest in the human genome. Over 6,000 mutations are known, and the gene has a relatively high natural mutation rate, with approximately 1 in 3 DMD cases arising due to a de novo mutation. There is no one mutation that is highly prevalent, and this factor provides a considerable challenge for therapeutics looking to target the root genetic cause of this debilitating disease.

That said, mutations in the dystrophin gene are not random, with hotspots of mutations existing between exons 45-53 and to a lesser extent between exons 2-20. It is thought that 13% of patients with DMD have mutations that are amenable to treatment with an exon 51-skipping approach, and thus the estimated exon 51 patient population is approximately 2,000 in the U.S., 3,200 in Europe and 700 in Japan.

Breakdown of DMD population by amenability to treatment with exon skipping therapeutics.

Current Approaches and Unmet Needs

There is no cure for DMD and approved exon-skipping therapies or advanced stage exon-skipping investigational candidates for patients who are amenable to exon 51 skipping are thought to have limited impact on disease progression due to low levels (<5%) of unadjusted dystrophin production. Corticosteroids are the mainstay of pharmacologic treatment for DMD as they have been shown to temporarily improve muscle strength, prolong the period of ambulation and slow the progression of this disease. However, glucocorticoid use is associated with well-known adverse effects, such as weight gain, stunted growth, weakening of bone structure, high blood pressure, diabetes, psychological effects, skin thinning and an increased risk of infection.

Several approaches have been taken to address groups of mutations in the dystrophin gene, one of which is to alter the processing of the dystrophin mRNA. A number of DMD patients suffer from mutations that result in the disruption of the reading frame of the DMD transcript, which in turn leads to an absence of the dystrophin protein. Using an ASO, the mRNA splicing process in the nucleus can be altered to skip over a select exon, allowing the open reading frame to be restored. This exon skipping approach

results in the subsequent generation of dystrophin protein isoform which, although internally deleted, retains much of its function and can thus protect muscle tissue against further contraction-induced damage.

Several unconjugated, or “naked” ASOs have been approved to treat DMD, including eteplirsen, marketed as EXONDYS 51 by Sarepta for the treatment of mutations amenable to an exon 51-skipping approach. This drug received accelerated approval from the FDA on the basis of an increase of less than 1% in the expression of dystrophin, with this readout being considered a valid surrogate endpoint under the accelerated approval regulatory pathway. Published observational studies of small numbers of patients on EXONDYS 51 appear to show somewhat slower disease progression than historical controls. However, at this level of dystrophin, this therapeutic has yet to formally establish evidence of clinical benefit through rigorously powered and adequately controlled clinical trials with functional endpoints. EXONDYS 51 has not been approved in Europe, or in Japan on the basis of this minimal degree of dystrophin restoration as a surrogate endpoint. Several companies are also developing antibody-oligonucleotide conjugates with the aim of enhancing the delivery and activity of their cargo therapeutics. These groups utilize both antigen-binding fragments, or Fabs, and monoclonal antibodies, or mAbs, as delivery vectors, to target specific cell surface receptors. We believe our EDO platform offers significant potential benefits over such approaches.

In addition, several companies are developing gene therapies to treat DMD. These include Sarepta’s SRP-9001 (marketed as ELEVIDYS®), which was originally approved by the FDA in June 2023 for the treatment of ambulatory pediatric patients aged 4 through 5 years with DMD with a confirmed mutation. In June 2024, the FDA granted approval of an expansion to the labeled indication for ELEVIDYS to include individuals with DMD with a confirmed mutation in the DMD gene who are at least 4 years of age, granting traditional approval for ambulatory patients and accelerated approval for non-ambulatory patients. Continued approval for non-ambulatory DMD patients may be contingent upon verification of clinical benefit in a confirmatory trial. There are additional investigational gene therapy programs in different stages of development to treat DMD. It is important to note that adeno-associated virus, or AAV-based gene replacement approaches deliver a significantly truncated dystrophin (micro-dystrophin) which we believe has the potential to limit the therapeutic efficacy of the approved and clinical stage AAV-based pipeline candidates. In addition, there are gene editing treatments that are in preclinical development. Exon skipping does not face some of the inherent challenges associated with gene therapy modalities, including:

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Limited packaging size of AAV vectors, resulting in the need to employ truncated ‘micro-dystrophin’ genes with an unclear functional benefit, where >70% of the dystrophin gene is omitted, including regions that correspond to key structural and binding domains;

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Increased safety concerns with high-dose AAV-based gene therapies (e.g., complement activation);

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Immunogenicity of AAV, resulting in:

Up to half of all patients possessing antibodies against the most commonly used recombinant AAV vector serotypes, precluding their eligibility for treatment;

Production of anti-AAV antibodies in treated patients, resulting in an inability to re-dose; and

Loss of gene copies over time as patients mature and their cells divide, reducing the durability of therapeutic effect; and

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Complexity and challenges inherent to manufacturing of AAV-based therapies.

We are also aware of several companies targeting non-dystrophin mechanisms for the treatment of DMD.

We believe that an exon skipping approach aimed at producing functional, truncated dystrophin will be a cornerstone approach to effectively treat patients with DMD.

Our Approach

We are developing or evaluating product candidates for the treatment of DMD in which exon skipping PMOs are conjugated to our EDO peptide in order to enhance their delivery to muscle cells. Our initial product candidate is PGN-EDO51, an investigational EDO peptide-conjugated exon 51-skipping ASO with a proposed mechanism of action we believe to be identical to that of eteplirsen.

PGN-EDO51 is designed to facilitate the skipping of exon 51, allowing the synthesis of a shortened, but functional, dystrophin.

The key differentiator between PGN-EDO51 and other exon 51-skipping approaches is the greater exon skipping activity observed with PGN-EDO51 in HVs, in early data from DMD patients, and in preclinical models. We believe the higher levels of exon skipping observed with PGN-EDO51 in HVs and in early data from DMD patients when compared to publicly available data from other therapies is directly related to the potential of our EDO platform to drive superior cellular uptake and nuclear delivery of the PMO cargo therapeutic resulting in exon skipping of the defective dystrophin mRNA.

Our Preclinical Data

We have evaluated the pharmacology of PGN-EDO51 in a number of in vitro and in vivo preclinical studies and have observed robust activity in every model system evaluated.

We conducted a repeat-dose study where we dosed mdx mice with 30 mg/kg of PGN-EDO23, a murine analogue of PGN-EDO51, every four weeks, with up to four doses, with tissue collection and analysis four weeks following the final dose. In the biceps, dystrophin production was measured by western blot and was observed to reach a mean level of 82.2% in the same tissue after four doses in comparison to a level of 22.5% obtained after a single dose. We believe this marked increase of 3.7 times between the level of dystrophin obtained following one dose, and the level obtained following four doses supports the clinical potential of a once-every-four-week dosing regimen for PGN-EDO51 and serves to highlight our belief that dystrophin production is likely to increase with additional doses over a longer treatment period.

In addition, in this repeat dosing study in mdx mice, dystrophin protein localization and the percent dystrophin positive fibers, or PDPF, were evaluated by immunofluorescence microscopy. Importantly, this orthogonal assessment of dystrophin demonstrated that dystrophin protein was uniformly distributed across the skeletal muscle sarcolemma and found 97.1% of biceps muscle fibers were

dystrophin positive following four doses of PGN-EDO23 administered once every four weeks, which was close to wild type, or WT, dystrophin levels (>99%).

Dystrophin levels and distribution in skeletal muscle with repeat dosing of PGN-EDO23 in mdx mice. Dystrophin protein evaluation by western blot and immunofluorescence (IF). Graph is presented as mean ± SD; n = 4-5 per cohort; grey band is dystrophin LLOQ (2.5%).

We have also conducted a number of studies in NHPs and have observed the robust in vivo activity of PGN-EDO51 in this higher order animal model. There is complete homology of the oligonucleotide binding site between the DMD gene in humans and the DMD gene in NHPs for an exon 51-skipping therapeutic, thus allowing the activity of our clinical candidate to be assessed in this species.

For example, following three bi-weekly doses of 30 mg/kg, we observed robust exon skipping activity for PGN-EDO51, with mean levels of greater than 70% obtained in key skeletal muscles following analysis by RT-PCR seven days after the final dose. In biceps, a mean exon 51 skipping level of 77.5% was obtained; and in quadriceps, 73.4%. We observed mean exon 51 skipping levels of over 20% in the left ventricle for PGN-EDO51, and 75.9% in the diaphragm, and we believe that these results highlight the potential of PGN-EDO51 to address the key cardio-respiratory morbidities affecting multiple organs observed in DMD.

Repeat dose administration of PGN-EDO51 in NHPs yielded high exon skipping rates in the key skeletal muscles, including the diaphragm, and in the cardiac left ventricle. Graph plotted as mean ± SD; n = 3 per group; study was not powered for statistical significance.

We have completed a number of Good Laboratory Practice, or GLP, studies that support a generally well-tolerated safety profile for PGN-EDO51, including repeat-dose NHP studies of PGN-EDO51. In one such study, we administered 11 doses of PGN-EDO51 intravenously to NHPs at 45 mg/kg over 60 minutes every 28 days over 39 weeks, and serum chemistry markers were assessed. Following the first administration, an elevation in serum creatinine was observed at day two; this elevation was completely resolved by day eight. Importantly, there were no adverse findings in the kidney even after 11 doses and there were no notable hematologic, cardiovascular or hepatic effects in this study. Additionally, following subsequent administrations, the day two elevations seen after the first dose were of lower magnitude. We believe these data support an acceptable tolerability profile for the ongoing CONNECT1 and CONNECT2 clinical studies.

Clinical Development

Phase 1 HV Study

In 2022, we completed a first-in-human, Phase 1, single-center, randomized, double-blind, placebo-controlled, SAD clinical trial to assess the target engagement (exon skipping), pharmacokinetics (oligonucleotide tissue concentration), safety and tolerability of PGN-EDO51 administered intravenously to 32 healthy adult male volunteers. Following administration, safety data were evaluated by a safety review committee prior to progressing to the next dose level. Volunteers were dosed with either 1, 5, 10 or 15 mg/kg of PGN-EDO51 or placebo. Oligonucleotide tissue concentration and exon skipping were assessed from needle biopsies of biceps muscle taken on days 10 and 28, with the latter being measured by a ddPCR assay.

A dose-dependent increase in mean exon skipping was observed in biceps.

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In the 10 mg/kg dose cohort, PGN-EDO51 exhibited mean exon skipping of 1.4% in biceps biopsies taken at day 28 (n=6).

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In the 15 mg/kg dose cohort, PGN-EDO51 exhibited mean exon skipping of 2.0% in biceps biopsies taken at day 28 (n=6).

A dose-dependent increase in PGN-EDO51 tissue concentration was observed in biceps.

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In the 10 mg/kg dose cohort, PGN-EDO51 exhibited mean oligonucleotide tissue concentrations of 11 nM in biceps biopsies taken at day 28 (n=6).

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In the 15 mg/kg dose cohort, PGN-EDO51 exhibited mean oligonucleotide tissue concentrations of 50 nM in biceps biopsies taken at day 28 (n=6).

We believe that the exon skipping data obtained from HVs in this clinical trial indicate the potential for clinically meaningful accumulation of exon 51-skipped transcripts and dystrophin in patient tissue with repeated doses of PGN-EDO51. Thus, based on these data, we anticipate that the exon skipping rates afforded by PGN-EDO51 when administered to patients have the potential to exceed the rates observed when administered to HVs. We believe the initial data from our CONNECT1 Phase 2 study, described below, further supports this potential.

The Phase 1 trial met its primary endpoint, providing evidence that PGN-EDO51 was observed to be generally well-tolerated at potentially clinically relevant dose levels. By way of example, at a dose of 10 mg/kg:

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All participants completed the study with no discontinuations;

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All related treatment-emergent adverse events, or TEAEs, including transient, reversible changes in kidney biomarkers, were assessed as mild and resolved without any intervention;

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Serum cystatin C, the recommended biomarker to assess renal function in DMD, did not change; and

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There was no evidence of hypomagnesemia.

At 15 mg/kg there was one non-life threatening serious adverse event, or SAE, related to changes in kidney biomarkers that were transient and reversible. This HV was admitted to the hospital for less than 24 hours, received hydration and then was re-admitted to the Phase 1 unit and completed the study. There were no clinical symptoms of acute kidney injury in any of the subjects. We also observed transient mild (Grade 1) hypomagnesemia in one participant and moderate (Grade 2) hypomagnesemia in one participant at the 15 mg/kg dose that did not require any intervention.

Under the Phase 1 protocol for PGN-EDO51, any non-life-threatening SAE was considered a dose-limiting toxicity, or DLT, however the study was not halted by the safety review committee, nor was it put on hold by Health Canada. In light of higher than anticipated oligonucleotide levels and exon skipping levels in muscle observed at 5 mg/kg and 10 mg/kg, we determined that further dose escalation in the Phase 1 study was not necessary.

CONNECT1 and CONNECT2 Phase 2 MAD Studies

The results from our Phase 1 HV clinical trial, together with the experience and expertise of our clinical development team and scientific advisory board, as well as learnings from previous clinical studies conducted in exon 51 skipping-amenable DMD patients, have guided the design, parameters and objectives of our planned Phase 2 clinical trials of PGN-EDO51 in DMD patients amenable to an exon 51-skipping approach.

The Phase 2 clinical development plan for PGN-EDO51 consists of two studies conducted in parallel; a smaller open-label MAD study, CONNECT1, is being conducted in Canada. A larger, randomized, double-blind placebo-controlled MAD study, CONNECT2, is open in the U.K., with plans to evaluate opening the study in other geographies subject to regulatory authorizations. In December 2024, we announced that we received a clinical hold notice from the FDA regarding our IND application to initiate the CONNECT2 study in the U.S. We are working with the FDA to address its questions regarding supportive data for the dosing levels planned for the patient population.

In the CONNECT1 study, PGN-EDO51 is being administered once every four weeks at 5 mg/kg and 10 mg/kg for 12 weeks. Dose escalation is based on data review by a data safety monitoring board, or DSMB. We are conducting muscle biopsies at baseline and initially, week 13, amended to week 16 for the 10 mg/kg cohort. In addition to assessing safety and tolerability, we are measuring exon skipping and dystrophin expression in CONNECT1. At the end of the CONNECT1 study period, participants have the option to enroll in the LTE phase of the study. We began dosing participants in our CONNECT1 study in early 2024 and in July 2024, we reported initial data from the 5 mg/kg starting dose cohort (n=3), as follows:

Exon Skipping. PGN-EDO51 produced mean exon skipping in biceps tissue of 2.15% at week 13 compared to baseline, measured by RT-PCR after four doses and three months of treatment. All participants demonstrated increased levels of exon skipping following treatment with PGN-EDO51, and we believe exon skipping will continue to increase with higher doses over a longer treatment period.

Dystrophin Production. PGN-EDO51 achieved a mean muscle-adjusted dystrophin level of 1.49% of normal (0.70% increase from baseline) and a mean absolute dystrophin level (by Western blot analysis) of0.61% of normal (0.26% increase from baseline), in each case after four doses, measured at week 13. All participants demonstrated increased dystrophin production following treatment with PGN-EDO51. With a longer treatment period and higher doses of PGN-EDO51, we expect to see higher levels of exon skipped transcript potentially resulting in significant increases in dystrophin.

Muscle Concentration. Consistent with the observed levels of exon skipping and dystrophin, treatment with PGN-EDO51 resulted in ~30nM of oligonucleotide in the muscle.

As of January 23, 2025, all three participants in the 5 mg/kg cohort were continuing to be dosed with PGN-EDO51 at 5 mg/kg in the LTE phase of the clinical trial.

Based on learnings from the 5 mg/kg cohort, we have amended the CONNECT1 study protocol. The changes include adjusting the timing for the final biopsy from day 7 to day 28, as noted above, adjusting the Performance of Upper Limb, or PUL, test entry score from three to four for inclusion, and adjusting the eligible age group from eight years of age and older to six - 16 years of age. We also expanded the 10 mg/kg cohort from three to four participants.

In December 2024, we announced that the 10 mg/kg cohort of CONNECT1 was fully enrolled (n=4). As of January 23, 2025, a total of 17 doses had been administered at 10 mg/kg in the ongoing study. Based on the totality of data in both the 5 mg/kg cohort and the ongoing 10 mg/kg cohort in the CONNECT1 trial as of January 23, 2025, we continue to believe PGN-EDO51 has a favorable emerging safety profile. Magnesium levels in two of the participants in the 10 mg/kg cohort, who were previously reported as having asymptomatic hypomagnesemia, have returned to levels within normal limits with administration of ongoing low-dose oral magnesium supplementation. Dosing of one of these two participants was paused due to a reduction of his estimated glomerular filtration rate, or eGFR. This event did not meet the pre-specified criteria for a DLT. A subsequent nuclear scan indicated measured glomerular filtration rate was in the normal range. The participant’s eGFR is improving and the investigator is evaluating for the resumption of dosing as this value returns to baseline levels. We are continuing to review the event and associated potential

confounding factors to better understand its manifestation. There have been no treatment-related SAEs, and all treatment-related adverse events have been mild. There was no sustained elevation in kidney biomarkers. There were also no cases of hypokalemia, anemia or thrombocytopenia. We expect to report clinical data from the 10 mg/kg cohort by the end of the third quarter of 2025.

We have received communication from Health Canada that dosing of participants in the 5 and 10 mg/kg cohorts may continue at their current dose levels. Health Canada has requested additional information from us to address its safety concerns before any further dose escalation or enrollment of any additional participants at the current dose levels. We are working with Health Canada to address its questions.

As noted above, we have opened the CONNECT2 study in the U.K. CONNECT2 will enroll approximately 20 ambulatory and non-ambulatory boys and young men living with DMD amenable to exon 51 skipping, who are at least six years of age. Participants will receive seven doses of either PGN-EDO51 or placebo at approximately four-week intervals for 24 weeks. Based on the data from CONNECT1, including PGN-EDO51’s favorable emerging safety profile to date, we have optimized the design of the CONNECT2 trial.

The starting dose of CONNECT2 was amended in the U.K. to be 10 mg/kg with escalation to potentially higher doses (if needed). Dose escalation will be determined based on data review by the DSMB. We will conduct muscle biopsies at baseline and at week 28. We will assess safety, tolerability, exon skipping, dystrophin production and functional outcome measures in this study.

As noted above, in December 2024, we announced that we received a clinical hold notice from the FDA regarding our IND application to initiate the CONNECT2 study in the U.S. We are working with the FDA to address its questions regarding supportive data for the dosing levels planned for the patient population. In parallel, we are evaluating opening CONNECT2 in other geographies outside of the U.S., subject to regulatory authorizations.

The CONNECT2 study, together with data from the CONNECT1 study, is intended to support a potential accelerated approval pathway for PGN-EDO51 with the FDA, subject to regulatory authority feedback.

PGN-EDODM1

Overview

We are developing PGN-EDODM1, an EDO peptide-conjugated PMO, for the treatment of DM1, a debilitating genetic disease with no approved therapies. PGN-EDODM1 leverages the same EDO peptide as PGN-EDO51 to deliver a PMO into muscle cells that binds to the pathogenic CUG trinucleotide repeat expansion present in the DMPK mRNA, thus reducing the ability of these trinucleotide repeats to sequester RNA binding proteins like MBNL1, a critical RNA processing protein. This approach, which is not designed to knock down DMPK, directly addresses the underlying genetic defect of this disease, and we have observed robust levels of activity in preclinical models with both long and short CTG repeats. In DM1 patient cells, we observed that treatment with PGN-EDODM1 led to a reduction in toxic nuclear foci, and liberated bound MBNL1 which mediated robust correction of mis-splicing. In preclinical studies in the mouse HSALR DM1 model, multiple monthly doses of PGN-EDODM1 corrected 99% of transcript mis-splicing and myotonia.

On February 24, 2025, we reported initial data from our FREEDOM Phase 1, randomized, placebo-controlled SAD clinical trial of PGN-EDODM1 in DM1 patients. We believe these data demonstrate that PGN-EDODM1 has a favorable emerging safety profile. Robust splicing correction in a dose-dependent manner was observed in the 5 and 10 mg/kg dose cohorts at day 28 after treatment with a single dose of PGN-EDODM1. The 15 mg/kg cohort is currently enrolling participants and we have begun dosing at this level. We anticipate reporting data from this cohort in the second half of 2025. We also initiated our FREEDOM2 Phase 2 randomized, double blind, placebo-controlled MAD study in DM1 patients in the U.K. and Canada in the second half of 2024. We are currently dosing participants in the 5 mg/kg dose cohort of this study and we expect to report data from this cohort in the first quarter of 2026.

The FDA has granted both orphan drug designation and Fast Track designation for PGN-EDODM1 for the treatment of DM1.

Disease Background and Prevalence

DM1 is a monogenic, autosomal dominant, progressive disorder that primarily affects skeletal, cardiac and smooth muscles, with central nervous system, or CNS, symptoms also being evident. Globally, the prevalence of DM1 is estimated to be 1 in 8,000 people, with approximately 40,000 patients in the U.S., 75,000 patients in Europe and 15,000 patients in Japan. However, under- and misdiagnosis is believed to be widespread, and genetic screening studies for DMPK triplet repeats have suggested that the prevalence of DM1 may be as high as 1 in 2,100 people.

DM1 patients can suffer from various manifestations of disease including myotonia, or a temporary rigidity due to the inability to relax muscles, muscle weakness, cardiac abnormalities, respiratory problems, fatigue, gastrointestinal complications, early cataracts, and cognitive and behavioral impairments. For patients with more severe forms of DM1, life expectancy is reduced due to increased mortality rates resulting from pulmonary and cardiac complications.

The broad spectrum of pathologies associated with DM1 arise due to genetic changes in the DMPK gene. Specifically, DM1 is caused by an expansion in the number of CTG triplet repeats that are present in the non-coding region of the DMPK gene, and following transcription this mutant DMPK gene yields an mRNA product with an expanded CUG repeat region. Healthy, asymptomatic individuals possess between 5 and 37 such repeats, but in DM1 patients the number of repeats can be in the thousands. These highly repetitive sequences form stable hairpin structures in the nucleus of cells and sequester critical RNA splicing proteins, such as MBNL1, leading to the formation of nuclear foci. The sequestration of MBNL1 prevents this key protein from performing its

normal function of processing RNA molecules before they are exported from the nucleus, leading to downstream mis-splicing events in a number of other transcripts. The mis-splicing of these transcripts results in the dysregulation of a broad set of downstream proteins, which in turn leads to in the multi-systemic pathologies that are associated with DM1, which include:

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Musculoskeletal: Myotonia (a temporary inability to relax a muscle after contraction), muscle weakness & wasting.

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Cardiac: Conduction defects.

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Respiratory: Breathing difficulties, sleep apnea.

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Gastrointestinal: Dysphagia (difficulty swallowing), constipation, Irritable Bowel Syndrome.

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CNS: Cognitive impairments, behavioral / psychologic disorders, excessive daytime sleepiness.

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Vision: Early-onset cataracts, retinal damage.

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Endocrine: Thyroid dysfunction, diabetes.

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Other pathologies: Skin, immune system and reproductive pathologies, increased cancer risk.

There is a general correlation between the number of CTG repeats in the aberrant DMPK gene and the severity of disease. Individuals with 50 to 150 repeats are prone to development of mild myotonia and cataracts, but typically have a normal lifespan. Individuals with up to approximately 1,000 repeats typically have muscle weakness and cardiac arrhythmia, with an average lifespan of 48 to 55 years. The most serious cases of DM1 are generally observed in individuals with more than 1,000 repeats, and these patients are likely to also suffer from respiratory defects and intellectual disability, with a shortened lifespan of approximately 45 years. Genetic anticipation is also observed, whereby the age of onset decreases in subsequent generations due to expansion of the CTG repeat between generations.

Current Approaches and Limitations

There are no approved therapies to treat DM1, with current standards of care being medicines that are used off-label for symptom management. Previously, a phosphorothioate ASO designed to cause degradation of the DMPK transcript was clinically assessed as a therapeutic for DM1. However, this therapeutic approach was restricted by the inefficiency of ASO delivery into target tissues and cells, thus limiting the effective clinical translation of this product candidate.

There are several clinical-stage approaches leveraging antibody-oligonucleotide conjugate, or AOC, technologies, that are currently in development for the treatment of DM1. These approaches utilize mAbs and Fabs that target the transferrin receptor 1, or TfR1, in order to deliver cargo oligonucleotides that are designed to knockdown or degrade DMPK. Such knockdown or degradation approaches cannot differentiate between expanded and non-expanded transcripts. In contrast to knockdown or degradation of overall DMPK levels, our approach is more targeted as PGN-EDODM1 is designed to disrupt the binding of MBNL1to the DMPK transcript. This approach maintains overall DMPK levels and thereby averts any potential for haploinsufficiency, a condition where a copy of the gene is deleted or mutated and the remaining copy is unable to produce sufficient protein for normal function. Furthermore, the correlation between the level of DMPK knockdown and the level of splicing correction required for therapeutic benefit is currently unclear, a consideration that may confound clinical development of these approaches. Therefore, we believe that PGN-EDODM1 is differentiated relative to the DMPK knockdown approaches in development for DM1 given its mechanism of action that is intended to bind DMPK, allowing release of MBNL1 to restore splicing and downstream functional effects. In addition, in preclinical studies and early clinical studies, the EDO platform has shown successful delivery of therapeutic PMOs to the nucleus, which we believe is critical to drive the anticipated therapeutic benefit of PGN-EDODM1.

We are also aware of another CPP approach conjugated to a PMO that is designed to block the CUG repeats in the DMPK transcript that is being evaluated in a Phase 2 study in patients with DM1.

Our Approach

Our product candidate for the treatment of DM1, PGN-EDODM1, consists of our lead EDO CPP conjugated to an ASO that binds to the pathogenic CUG repeat expansion in the DMPK mRNA. We are employing the same EDO peptide in PGN-EDO51 and PGN-EDODM1. PGN-EDODM1 is designed to directly address the deleterious effects of genetic alteration in DM1, specifically the sequestration of MBNL1 due to the high number of CUG repeat expansion in the DMPK transcript.

We believe that this innovative therapeutic approach has considerable advantages over oligonucleotide modalities that rely on knockdown or degradation of the DMPK transcript. PGN-EDODM1 disrupts the binding between the CUG repeat expansion and MBNL1, an approach which we believe will allow the DMPK transcript to continue performing its normal function within the cell,

while also liberating MBNL1 to correct downstream mis-splicing events. We believe that this therapeutic strategy positions us to potentially provide clinically meaningful benefits for DM1 patients while mitigating the risk of potential deleterious outcomes.

PGN-EDODM1 is designed to bind to the CUG repeats in DMPK RNA and liberate MBNL1 to restore physiological splicing, in contrast to modalities that indiscriminately target both normal and pathogenic DMPK for degradation.

Preclinical Data

In an in vitro study utilizing DM1 patient cells with approximately 2,600 CTG repeats in the DMPK gene, we observed a robust reduction in nuclear foci, liberation of MBNL1 from foci and the correction of downstream transcript mis-splicing pathologies. In this study, immortalized myoblasts from a DM1 patient were differentiated for four days, and then treated for 24 hours with PGN-EDODM1 at a range of concentrations from 0 μM to 20 μM. Myoblasts from a healthy individual were utilized as a control, and the unconjugated PMO was also assessed at a concentration of 20 μM in this study in order to demonstrate the critical role that our EDO platform plays in driving efficient cell uptake of this therapeutic cargo.

A characteristic feature of DM1 is the accumulation of nuclear foci, or myonuclear aggregates of DMPK mRNA bearing the pathogenic CUG repeat expansion. These foci sequester MBNL1, a critical modulator of transcript splicing, and thus play a key role in the downstream spliceopathies that are observed in this multi-systemic disorder. We assessed the impact of PGN-EDODM1 treatment on the presence of nuclear foci in DM1 cells through visualization with fluorescence in situ hybridization, or FISH, and immunofluorescence co-staining, and we observed that treatment led to a robust mean reduction of 54% in the number of these toxic aggregates. In contrast, treatment with the unconjugated PMO cargo did not yield a reduction in nuclear foci, an observation which we believe supports the potential utility of our EDO platform in driving the successful delivery of therapeutic agents to their nuclear site of action.

In this same in vitro study, we also assessed the impact of PGN-EDODM1 treatment on the sequestration of MBNL1. Following treatment and visualization, we observed a mean reduction in the amount of foci-bound MBNL1, indicating that that this critical splicing factor is liberated upon treatment with our DM1 product candidate. We believe these results provide additional support for the proposed mechanism of action of PGN-EDODM1, suggesting that – once delivered to the cell nucleus – our therapeutic cargo may bind to the CUG repeat expansion present in the DMPK transcript, resulting in a reduction in the number of nuclear foci and the liberation of MBNL1.

Furthermore, treatment of DM1 patient cells with PGN-EDODM1 led to robust correction of downstream mis-spliced transcripts associated with key disease pathologies in a dose-dependent fashion. At the highest dose assessed, 20 μM, PGN-EDODM1 treatment resulted in robust mis-splicing correction, resulting in mean exon inclusion or exclusion rates of approximately 70% of healthy control levels in these transcripts. We believe this observation supports our therapeutic hypothesis that treatment with

PGN-EDODM1 may restore the altered global spliceopathy profiles seen in DM1 patients, thus ameliorating the key pathologies that are the hallmark of this devastating disease.

PGN-EDODM1 Reduced Pathogenic Nuclear Foci, Liberated MBNL1 and Corrected Mis-Splicing in Patient Cells with Long CUG Repeats. Immortalized myoblasts from healthy individuals or DM1 patients were cultured then differentiated for four 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.

Building on the encouraging positive data from our in vitro studies, we utilized the HSALR mouse model of DM1 to assess the activity of PGN-EDODM1. This transgenic mouse model contains between 220 and 250 CTG trinucleotide repeats in the inserted human skeletal actin, or HSA, gene, and exhibits molecular and functional pathologies that are very similar to those seen in human DM1 patients. The CUG repeat expansion present in the HSALR mouse model, and the subsequent sequestration of MBNL1, leads to downstream defects in the normal mRNA splicing patterns for a number of transcripts, resulting in aberrant inclusions or exclusions of exons. Sequestration of MBNL1 in the HSALR mouse model causes mis-splicing of multiple RNAs. This mis-splicing causes the mice to exhibit myotonia, effectively recapitulating the classic symptom of disease that is observed in DM1 patients.

We dosed HSALR mice with one or four doses of PGN-EDODM1, with four-week intervals between doses. Skeletal muscle tissues were collected four weeks post-final dose. Skeletal muscle tissue concentration was measured by fluorescent based HPLC method. Following multiple doses of PGN-EDODM1 at 30 mg/kg given once every four weeks, PGN-EDODM1 produced a mean 99% correction of mis-splicing and a mean 99% correction of myotonia.

PGN-EDODM1 demonstrated enhanced efficacy in terms of splicing correction and improvement in myotonia after repeat doses vs. single doses in preclinical study in HSALR mice HSALR mice.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 four 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. Graph is presented as mean ± SD; n = 12-43 per cohort.

We have completed a number of GLP studies that support a generally well-tolerated safety profile for PGN-EDODM1. , including repeat-dose NHP studies of PGN-EDODM1. In one such study, we administered 11 doses of PGN-EDODM1 intravenously to NHPs, 10 of which were at 45 mg/kg, over 60 minutes every 28 days over 39 weeks, and serum chemistry markers were assessed. Following the first administration, an elevation in serum creatinine was observed at day two; this elevation was completely resolved by day eight. Following repeat-dose administrations of 45 mg/kg, the transient elevations in creatinine were of comparable magnitude, i.e., did not worsen. Importantly, there were no adverse findings in the kidney even after 11 doses and there were no notable hematologic, cardiovascular or hepatic effects in this study. We believe these data support an acceptable tolerability profile for the ongoing FREEDOM and FREEDOM2 clinical studies.

Clinical Development

Our clinical development program for PGN-EDODM1 includes two studies, FREEDOM, a multinational, randomized, double-blind, placebo-controlled Phase 1 SAD study, and FREEDOM2, a multinational, randomized, double blind, placebo-controlled Phase 2 MAD study. In the FREEDOM study, we intend to enroll up to approximately 32 adult participants with DM1 in multiple geographies including the U.S., U.K. and Canada, to evaluate the safety and tolerability of PGN-EDODM1. Per the protocol, PGN-EDODM1 was administered at starting doses of 5 mg/kg and 10 mg/kg with subsequent dose escalation to 15 mg/kg, and potentially in the future to 20 mg/kg, based upon evaluation by a DSMB of safety data from the prior dose cohort(s). We are conducting muscle biopsies at baseline, at day 28 and at week 16. In addition to safety and tolerability, we are assessing oligonucleotide muscle concentrations, splicing correction and functional outcome measures at day 28 and at week 16 following a single dose of PGN-EDODM1.

On February 24, 2025, we reported initial data from the 5 mg/kg and 10 mg/kg dose cohorts of the FREEDOM study. We believe PGN-EDODM1 has a favorable emerging safety profile. Through the data cutoff date of December 3, 2024, PGN-EDODM1 was observed to be generally well-tolerated, with most TEAEs being mild or moderate in severity. There were three SAEs, one of which was related to study drug (abdominal pain, 10 mg/kg) that was potentially confounded by use of a prohibited, off-label drug taken on the morning of PGN-EDODM1 dosing. Other SAEs included appendicitis (5 mg/kg) and right anterior tibial artery pseudoaneurysm (10 mg/kg; in connection with biopsy procedure). Four participants experienced seven study drug related TEAEs, as follows: nausea (n=2); vomiting (n=1); dizziness (n=1); headache (n=1); feeling hot (n=1); abdominal pain (n=1). There were no adverse events related to electrolytes or renal biomarkers.

Muscle Tissue Concentration. Treatment with a single dose of PGN-EDODM1 resulted in a mean 13.7 ng/g and 44.1 ng/g of PGN-EDODM1 in the muscle at 5 mg/kg (n=6) and 10 mg/kg (n=5)1, respectively, at day 28 post-dosing, which is a greater than dose proportional increase in muscle concentration, which correlates with robust and dose-dependent splicing correction.

Splicing Correction. Following treatment with a single dose of PGN-EDODM1, a dose-dependent mean splicing correction from evaluable participants1,2 of 12.3% and 29.1% at 5 mg/kg (n=6) and 10 mg/kg (n=4), respectively, as measured by the 22-gene panel3, was observed at day 28 post-dosing.

Functional Outcomes.

10-Meter Walk Run Test/Myotonia (vHOT middle finger): While single-dose studies have not demonstrated improved functional outcomes in DM1 patients, we collected data from the 5 and 10 mg/kg cohorts that we believe showed positive early trends in some functional outcome measures. We believe robust splicing correction with PGN-EDODM1 has the potential to lead to meaningful functional improvements with repeat dosing over time.

One participant’s biopsy was not collected at day 28 due to pseudoaneurysm in connection with the biopsy procedure.

One participant’s sample at day 28 showed a splicing index outside the pre-specified assay range at baseline and day 28 (no detectable mis-splicing) and was excluded from the analysis.

Provenzano et al., The Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1, J Clin. Invest. 2025.

We expect to report data from the 15 mg/kg cohort of the FREEDOM study in the second half of 2025.

The safety data from the initial cohorts of the FREEDOM trial has informed the design of FREEDOM2 trial, which is currently open in Canada and the U.K. We also plan to open the FREEDOM2 study in other geographies, including the U.S., subject to regulatory authorizations. In the FREEDOM2 study, we intend to enroll approximately 24 adult participants with DM1 to evaluate the safety and tolerability of PGN-EDODM1. Per the protocol, PGN-EDODM1 is being administered at the starting dose of 5 mg/kg and will subsequently increase to 10 mg/kg and potentially 20 mg/kg, based upon evaluation by a DSMB of safety data from the prior dose cohort(s). Dosing will be administered every four weeks for a period of twelve weeks. We intend to conduct muscle biopsies at baseline and at week 16. In addition to safety and tolerability, we plan to assess oligonucleotide muscle concentrations, splicing

correction and functional outcome measures at week 16 following multiple doses of PGN-EDODM1. We expect to report data from the 5 mg/kg cohort of the FREEDOM2 study in the first quarter of 2026.

Based on the favorable emerging safety profile and robust initial splicing data from FREEDOM, we believe that PGN-EDODM1 has the potential to be disease-modifying and could improve outcomes for patients living with DM1.

Expanding the Application and Scope of Our EDO Platform

Additional DMD Patient Populations

We are also developing EDO therapeutics for additional DMD patient populations, including exon 53, 45 and 44. These programs utilize the same EDO CPP as PGN-EDO51. We plan to leverage significant learnings garnered from the preclinical and clinical development of PGN-EDO51 to advance one or more therapeutic candidates for additional DMD patient populations.

New Indications with PMO Therapeutics

In the future, we intend to apply our deep understanding of our EDO platform and PMO therapeutics to the development of additional product candidates in other indications. Based on extensive preclinical and early clinical data we have generated, we believe that the ability of our EDO peptides to deliver exon skipping and RNA blocking therapeutics to muscle cells and other target tissues positions us to develop additional product candidates in other neuromuscular indications as well as in potentially neurologic indications.

New Cargos

We believe that our EDO technology has the potential to facilitate the delivery of multiple types of oligonucleotide therapeutics. To date, our efforts have primarily focused on the delivery of PMOs, but we also intend to pursue the expansion of our cargo scope to other nucleic acid species.

New Peptide Technologies

We intend to further establish our expertise and competitive position in the field of oligonucleotide delivery through the ongoing research and development of new peptides. In connection with these efforts, we intend to leverage our deep expertise in this field to design new peptides that target specific tissue types, and to seek to further optimize the tissue and cellular delivery of our EDO platform.

Manufacturing

Our manufacturing process is modular in nature. The peptide and oligonucleotide components are assembled using readily available building blocks and are subsequently conjugated using well-established methodologies. This process is fully synthetic and does not rely on microbial fermentation, thus substantially reducing the risk of introducing microbial DNA or protein into our product candidates. Furthermore, our manufacturing process is scalable and easily characterizable – attributes that we intend to leverage to support the rapid development and clinical translation of our EDO conjugate therapeutics. We have produced, manufactured and released multiple batches under current Good Manufacturing Practice, or cGMP, and have successfully utilized this material in several clinical trials, including a completed Phase 1 HV study and ongoing Phase 1 and Phase 2 studies in patients.

We do not own or operate manufacturing facilities, and currently rely on third-party contract development manufacturing organizations, or CDMOs, for the CPP, linker and oligonucleotide components that comprise our EDOs, and for the conjugation of our product candidates as well as for the manufacturing of the finished dosage form (sterile injectable drug product). We anticipate that we will continue to utilize third-party CDMOs and suppliers to support our ongoing and future preclinical, clinical and commercial activities, and our intention is to build this network of organizations as we scale our manufacturing requirements. Long-term, we may also decide to establish internal manufacturing of our drugs or selected intermediates.

We believe that there are multiple sources for all raw materials employed in the manufacturing of our EDO therapeutics, and we believe that several CDMOs are able to assemble the peptide intermediate, the oligonucleotide intermediate and the final API.

There are extensive regulations that govern the manufacturing of pharmaceutical products, and the third-party manufacturing organizations we work with are required to adhere to these regulations. Our CDMOs are required to manufacture our product candidates under cGMP requirements, alongside other applicable laws and regulations.

Competition

The biopharmaceutical industry is characterized by the rapid evolution and development of new technologies, leading to an environment that is intensely competitive in nature and thus supports the robust protection and defense of intellectual property. Any EDO product candidates that we successfully develop and commercialize will compete both with existing therapeutics, and with new approaches that may arise in the future. While we believe that our unique EDO platform and extensive expertise in oligonucleotide delivery may provide us with a differentiated position in the neuromuscular and neurologic spaces, such competing technologies may

arise from many different sources, including large biopharmaceutical organizations, specialty pharmaceutical and biotechnology companies, academic institutions, government agencies, and public and private research organizations.

We expect to face competition from existing products and product candidates in development for each of our programs. Currently, patients with DMD are treated with corticosteroids to manage the inflammatory component of the disease. EMFLAZA® (deflazacort) is an FDA-approved corticosteroid marketed by PTC Therapeutics, Inc., or PTC. Individuals with DMD also use prednisone or prednisolone off-label. In addition, there are several FDA-approved exon skipping drugs: EXONDYS 51 and VYONDYS 53® (golodirsen), which are naked PMOs approved for the treatment of DMD patients amenable to exon 51 and exon 53 skipping, respectively, marketed by Sarepta; and VILTEPSO® (viltolarsen), a naked PMO approved for the treatment of DMD patients amenable to exon 53 skipping, which is marketed in the U.S. by NS Pharma, Inc. Notably, it was reported in May 2024 that the Phase 3, confirmatory study of VILTEPSO failed to meet the primary endpoint, Time to Stand from Supine, measured as velocity rise per second. Companies focused on developing treatments for DMD that target increased dystrophin expression, as our DMD program does, include Dyne Therapeutics, Inc., or Dyne, with DYNE-251, an antibody-conjugated PMO that targets exon 51 skipping in a Phase 1/2 clinical trial; BioMarin Pharmaceutical Inc., or BioMarin, with BMN-351, a phosphorothioate oligonucleotide that targets exon 51 skipping currently in preclinical development; and Wave Life Sciences Ltd., or Wave, with WVE-N531, a stereopure oligonucleotide in a Phase 1/2 clinical trial for patients amenable to exon 53 skipping. In November 2024, Sarepta announced it was discontinuing development of SRP-5051 (vesleteplirsen), a peptide-linked PMO for patients amenable to exon 51 skipping, based on the risk-benefit of the program, including some patients experiencing hypomagnesemia even after treatment discontinued, feedback from the FDA, and the evolving therapeutic landscape for DMD.

In addition, several companies are developing gene therapies to treat DMD. These include Sarepta’s ELEVIDYS which was approved in June 2023 for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD with a confirmed mutation in the DMD gene. In June 2024, the FDA granted approval of an expansion to the labeled indication for ELEVIDYS to include individuals with DMD with a confirmed mutation in the DMD gene who are at least 4 years of age, granting traditional approval for ambulatory patients and accelerated approval for non-ambulatory patients. Continued approval for non-ambulatory DMD patients may be contingent upon verification of clinical benefit in a confirmatory trial. In addition, several other companies are developing investigational gene therapies to treat DMD, including Solid Biosciences Inc.’s SGT-003 and REGENXBIO Inc.’s RGX-202, currently in Phase 1 and Phase 2 clinical development, respectively. Gene editing treatments that are in preclinical development are also being pursued by Vertex Pharmaceuticals, Inc., or Vertex, and Sarepta.

We are also aware of several companies targeting non-dystrophin mechanisms for the treatment of DMD, including Edgewise Therapeutics, Inc., or Edgewise, with EDG-5506, a muscle stabilizer that is currently in clinical development and Italfarmaco S.p.A., with DuvyzatTM (givinostat), an oral histone deacetylase, or HDAC, inhibitor, that reduces fibrosis in patients with DMD that was approved by the FDA in March of 2024 for the treatment of DMD in patients six years of age and older, and is under review by the EMA.

For DM1, there are currently no approved therapies to treat the underlying cause of the disease. Product candidates currently in clinical development to treat DM1 include several approaches that target DMPK RNA. These include AOC 1001, an antibody linked siRNA in Phase 3 clinical development by Avidity Biosciences, Inc., or Avidity; DYNE-101, an antibody conjugated antisense oligonucleotide in Phase 1/2 clinical development by Dyne; VX-670, a peptide conjugated PMO in Phase 2 by Entrada Therapeutics, Inc., or Entrada, and Vertex; and ARO-DM1, a conjugated siRNA in Phase 1/2 clinical development by Arrowhead Pharmaceuticals, Inc., or Arrowhead, and Sarepta. There are additional approaches under development such as ATX-01, a micro RNA that modulates the expression of MBNL1 by Arthex Biotech S.L. that is in Phase 1 development. Another small molecule, tideglusib, which is a GSK3-ß inhibitor is in clinical development by AMO Pharma Ltd., or AMO, for DM1.

Several gene editing and gene delivery treatments are in discovery or preclinical development by Vertex and Kate Therapeutics Inc. (recently acquired by Novartis); Design Therapeutics, Inc., or Design, is developing an approach to prevent formation of CUG hairpins; Expansion Therapeutics, Inc., or Expansion, and Arrakis Therapeutics, or Arrakis, are developing an approach utilizing the interaction of small molecules with RNA in preclinical development; and therapeutics based on biomolecular condensate biology are in preclinical development by Dewpoint Therapeutics, Inc., or Dewpoint, and Pfizer.

We will also compete more generally with other companies developing alternative scientific and technological approaches, including companies working to develop conjugates with oligonucleotides for extra-hepatic delivery, including Alnylam Pharmaceuticals, Inc., or Alnylam, Aro Biotherapeutics Co., or Aro, Arrowhead, Avidity, Dicerna Pharmaceuticals, Inc. (acquired by Novo Nordisk), or Dicerna, Dyne, Entrada, Ionis Pharmaceuticals, Inc., or Ionis. NeuBase Therapeutics, Inc., or NeuBase, PYC Therapeutics Limited, or PYC, and Sarepta, as well as gene therapy and gene editing approaches.

Many of the companies which we compete with or may compete with in the future have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Accordingly, our competitors may be more successful than us in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining approval for treatments and achieving widespread market acceptance, rendering our treatments obsolete or non-competitive.

Additionally, mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller and other early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

If we successfully obtain approval for any product candidate, we will face competition based on many different factors, including the safety and effectiveness of our products, the ease with which our products can be administered and the extent to which patients accept relatively new routes of administration, the timing and scope of regulatory approvals for these products, the availability and cost of manufacturing, marketing and sales capabilities, price, reimbursement coverage and patent position. Competing products could present superior treatment alternatives, including by being more effective, safer, more convenient, less expensive or marketed and sold more effectively than any of our products, if approved. Competitive products or technological approaches may make any products we develop, or our EDO platform, obsolete or noncompetitive before we recover the expense of developing and commercializing our product candidates. If we are unable to compete effectively, our opportunity to generate revenue from the sale of our products, if approved, could be adversely affected.

Sales and Marketing

We currently do not have a commercial infrastructure in any geography. As we progress our programs through development, we may build a commercial infrastructure in the U.S. and selected other territories to support the commercialization of each of our product candidates when we believe a regulatory approval in a particular territory is likely. We intend to conduct market research in connection with designing our commercialization strategy for each of our product candidates, which strategy may depend on the size and geographic dispersion of the target patient population and the characteristics of the prescribing audience for our products, if approved. For example, with respect to certain of our product candidates that target diseases with a limited patient population, a concentrated prescribing audience and a small number of key opinion leaders who influence the treatments prescribed for the relevant patient population, we may address each such market using our own targeted, specialty sales and marketing organization supported by internal sales personnel, an internal marketing group and distribution support. For other product candidates, we may establish a larger and more dispersed sales force, or seek strategic collaborations to support our commercialization efforts.

We intend to evaluate our commercialization strategy as we advance each product candidate through clinical development. In any core markets outside of the U.S. that we may identify, where appropriate, we may utilize strategic partners, distributors or contract sales forces to expand the commercial availability of our product candidates.

Material Contracts

License of Technology Agreement with Oxford University Innovation Limited and Medical Research Council as Part of United Kingdom Research and Innovation

On March 26, 2018, we, through our wholly-owned subsidiary PepGen Limited, entered into a license agreement, or the OUI/MRC License, with Oxford University Innovation Limited, or OUI, and MRC. We amended the OUI/MRC License on December 21, 2018, and subsequently amended and restated it on November 23, 2020.

Pursuant to the OUI/MRC License, we obtained from OUI and MRC an exclusive, royalty-bearing, sublicensable with consent (through one tier) license under certain patent rights, or the OUI/MRC Patents, and data, or the OUI/MRC Licensed Technology, and a nonexclusive, royalty-bearing, sublicensable (through one tier) license under certain know-how, or the OUI/MRC Know-How, for certain biological and chemical compounds, including compounds that comprise amino acids and/or nucleic acids relating to our EDO peptides, proprietary linkers and the resulting EDO conjugates. The Licensed Technology is incorporated in our product candidates PGN-EDO51, PGN-EDODM1, PGN-EDO53, PGN-EDO45 and PGN-EDO44, and will likely be utilized in future discovery programs. Under such licenses, we have the right to make, have made, import, use, sell, offer for sale, market, research, develop, trial, register, modify, enhance, improve, manufacture, have manufactured, hold, keep, formulate, optimize, have used, export, transfer, distribute, promote, have sold, dispose of, offer to dispose of or otherwise exploit in all fields of use on a worldwide basis any products or services that incorporate or otherwise utilize the OUI/MRC Licensed Technology or, in each such case, an OUI/MRC Licensed Product. We granted OUI, and those persons who at any time work or have worked on the OUI/MRC Licensed Technology and OUI/MRC Know-How, and MRC an irrevocable, perpetual, royalty-free, sublicensable license under the OUI/MRC Licensed Technology and OUI/MRC Know-How to use the OUI/MRC Licensed Technology and OUI/MRC Know-How for non-commercial clinical, research, teaching, publication, or other scholarly purposes, or Non-Commercial Purposes. MRC also retained the right to grant sublicenses under our rights in the OUI/MRC Licensed Technology and OUI/MRC Know-How for Non-Commercial Purposes to any person at MRC or any academic or not-for-profit institutions who have worked or collaborated on, or otherwise funded, the OUI/MRC Licensed Technology or OUI/MRC Know-How. Further, OUI, MRC and the Chancellor, Masters and Scholars of the University of Oxford retained the right to freely use, publish (subject to certain obligations) or grant licenses under the OUI/MRC Know-How.

The OUI/MRC License requires us to use commercially reasonable efforts to exploit the OUI/MRC Licensed Technology and to achieve certain development milestones in accordance with a development plan and commercialize the OUI/MRC Licensed Products.

In consideration for the rights conveyed by OUI and MRC under the OUI/MRC License, we were obligated to pay, and have paid, to OUI certain up-front fees in an aggregate amount of approximately £80,000 in connection with the execution of each of the original OUI/MRC License and the amended and restated OUI/MRC License. In addition, we are obligated to pay to OUI sub-single to low, single-digit percentage royalties, or the Royalty Rate, on net sales of any OUI/MRC Licensed Products in excess of a threshold amount between £20 million and £30 million that are commercialized by us. The royalty rate for a given OUI/MRC Licensed Product will decrease a certain percentage following expiration or revocation of the last valid claim of the OUI/MRC Patents covering such OUI/MRC Licensed Product and where there is a product sold by a third party that competes with such OUI/MRC Licensed Product on a country-by-country basis. If we receive any non-royalty payments and royalties in connection with sublicenses or other contracts

relating to the OUI/MRC Licensed Technology or OUI/MRC Know-How, we are obligated to pay to OUI, in each instance, a sublicense fee that is from mid-single digit to mid-teen percentage depending on the license year in which we execute the sublicense or contract. We are also required to pay certain milestone payments to OUI upon the achievement by us or our sublicensees of specified commercial milestone in an aggregate amount of £100,000 for certain OUI/MRC Licensed Products and specified patent procurement milestone in an aggregate amount of £10,000. In 2024, we paid OUI the patent procurement milestone of £10,000, adjusted per the retail price index under the terms of the OUI/MRC License.

Upon completion of our initial public offering, or IPO, in May 2022, we paid an exit fee of $1.4 million to OUI during the second quarter of 2022.

Unless earlier terminated, the OUI/MRC License will terminate in its entirety upon the later of (a) the date on which all patents and patent applications licensed to us under the OUI/MRC License have been abandoned or allowed to lapse or expired or been rejected or revoked without a right of further appeal in a relevant country or territory or (b) March 26, 2038. The last-to-expire licensed patent under the OUI/MRC License is set to expire on February 11, 2042. We may terminate the OUI/MRC License in its entirety at any time for convenience upon providing OUI and MRC with written notice. Either party may terminate the OUI/MRC License in its entirety for the other party’s uncured material breach after an opportunity for the other party to cure such material breach. OUI and MRC may terminate the OUI/MRC License for our (a) insolvency or if we challenge the validity of the licensed patents, (b) breach our obligation to develop and exploit the technology in accordance with the development plan and subsequent failure to take remedial action reasonably requested by OUI and/or MRC or (c) failure to pay the Exit Fee or Exit Buy Out Fee. If the OUI/MRC License is terminated by either party for any reason, the OUI/MRC Licenses will terminate and all rights thereunder will revert to OUI and MRC, respectively.

Intellectual Property

We seek to protect the intellectual property, or IP, and proprietary technology that we consider important to our business, including by pursuing patent applications that cover our product candidates and methods of using the same, as well as any other relevant inventions and improvements that are considered commercially important to the development of our business. We likewise seek to protect the IP to which we obtain rights through licenses and sublicenses (e.g., from universities and research institutions) and work collaboratively with our licensors to ensure (and if possible be the driver of) patent prosecution and protection. We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and IP positions. Our commercial success depends, in part, on our ability to obtain, maintain, enforce and protect our intellectual property and other proprietary rights for the technology, inventions and improvements we consider important to our business, and to defend any patents we may own or in-license in the future, prevent others from infringing any patents we may own or in-license in the future, preserve the confidentiality of our trade secrets, and operate without infringing, misappropriating or otherwise violating the valid and enforceable patents and proprietary rights of third parties.

As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position(s) for our product candidates and technologies will depend on our success in obtaining effective patent claims and enforcing those claims if granted. However, our pending patent applications, and any patent applications that we may in the future file or license from third parties, may not result in the issuance of patents and any issued patents we may obtain do not guarantee us the right to protect our technology in relation to the commercialization of our products. We also cannot predict the breadth of claims that may be allowed or enforced in any patents we may own or in-license in the future. Notwithstanding the scope of the patent protection available to us, a competitor could develop competitive products that are not covered by our intellectual property, and we may be unable to stop such competitor from commercializing such products.

Any issued patents that we may own or in-license in the future may be challenged, invalidated, circumvented or have the scope of their claims narrowed. Because patent applications can take many years to issue, there may be applications unknown to us, which applications may later result in issued patents that our existing or future products or technologies may be alleged to infringe. Additionally, we cannot be certain of the priority of inventions covered by pending third-party patent applications. If third parties prepare and file patent applications in the U.S. that also claim technology or therapeutics to which we have rights, we may have to participate in interference proceedings in the U.S. Patent and Trademark Office, or USPTO, to determine priority of invention, which is highly unpredictable and which could result in substantial costs, even if the eventual outcome is favorable to us. We are aware of certain patents in the U.S. and other jurisdictions owned by third parties that claim subject matter that relates to our product candidates and the EDO platform. In addition, because of the extensive time required for clinical development and regulatory review of a product candidate we may develop, it is possible that, before any of our product candidates can be commercialized, any patent covering a certain product may expire or remain in force for only a short period following commercialization, thereby limiting the protection such patent would afford the respective product and any competitive advantage such patent may provide.

The term of individual patents depends upon the date of filing of the patent application, the date of patent issuance and the legal term of patents in the countries in which they are obtained. In most countries, including the U.S., the patent term is 20 years from the earliest filing date of a non-provisional patent application. In the U.S., a patent’s term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the USPTO in examining and granting a patent or may be shortened if a patent is terminally disclaimed over an earlier expiring patent.

The term of a patent claiming a new drug product may also be eligible for a limited patent term extension when FDA approval is granted, provided statutory and regulatory requirements are met. The restoration period granted on a patent covering a product is typically one-half the time between the effective date of a clinical investigation involving human beings is begun and the submission date of an application, plus the time between the submission date of an application and the ultimate approval date. The restoration period cannot be longer than five years and the total patent term, including the restoration period, must not exceed 14 years following

FDA approval. Only one patent applicable to an approved product is eligible for the extension, and only those claims covering the approved product, a method for using it, or a method for manufacturing it may be extended. Additionally, the application for the extension must be submitted prior to the expiration of the patent in question. A patent that covers multiple products for which approval is sought can only be extended in connection with one of the approvals. The USPTO reviews and approves the application for any patent term extension or restoration in consultation with the FDA. In the future, if our product candidates receive approval by the FDA, we expect to apply for patent term extensions on any issued patents covering those products, depending upon the length of the clinical studies for each product and other factors.

There can be no assurance that our pending patent applications will issue or that we will benefit from any patent term extension or favorable adjustments to the terms of any patents we may own or in-license in the future. In addition, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent. Patent term may be inadequate to protect our competitive position on our products for an adequate amount of time.

In the future, we may need to engage in litigation to enforce patents issued or licensed to us, to protect our trade secrets or know-how or to defend against claims of infringement of the rights of others. Litigation could be costly and could divert our attention from other functions and responsibilities. Furthermore, even if our patents are found to be valid and infringed, a court may refuse to grant injunctive relief against the infringer and instead grant us monetary damages and/or ongoing royalties. Such monetary compensation may be insufficient to adequately offset the damage to our business caused by the infringer’s competition in the market. Adverse determinations in litigation could subject us to significant liabilities to third parties, could require us to seek licenses from third parties and pay significant royalties to such third parties and could prevent us from manufacturing, selling or using our product or techniques, any of which could severely harm our business.

As of December 31, 2024, we owned three pending U.S. patent applications, one pending Patent Cooperation Treaty, or PCT, international application, two European patent applications, two Japanese patent applications, two Hong Kong patent applications, one Canadian patent application, and one Chinese patent application, and we exclusively licensed one issued European patent (validated in France, Germany, Italy, Spain, and Great Britain), one Saudi Arabian patent, and 76 pending patent applications under our OUI/MRC License. For more information regarding our OUI/MRC License, see the section titled “Business—Material Contracts—License of Technology Agreement with Oxford University Innovation Limited and Medical Research Council as Part of United Kingdom Research and Innovation.”

The issued patent and patent applications that cover our product candidates and technology, as of December 31, 2024, include:

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With respect to PGN-EDO51, we owned applications pending in the U.S., Europe and Japan that cover methods of use and exclusively licensed 50 pending patent applications under the OUI/MRC License that cover compositions of matter and methods of use, including applications in Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, Mexico, New Zealand, the Russian Federation, Saudi Arabia, and the U.S. Any patents issuing from the patent applications would have expiration dates ranging from 2039 to 2042, without accounting for any available patent term adjustments or extensions.

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With respect to PGN-EDODM1, we owned applications pending in the U.S., Canada, China, Europe, Hong Kong, and Japan that cover methods of use and exclusively licensed one patent and 44 pending patent applications under the OUI/MRC License that cover compositions of matter and methods of use, including a patent in Saudi Arabia and applications in Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, Mexico, the Russian Federation, and the U.S. Any patents issuing from the patent applications would have expiration dates ranging from 2039 to 2042, without accounting for any available patent term adjustments or extensions.

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With respect to PGN-EDO53, PGN-EDO45 and PGN-EDO44, we owned one application pending in the U.S., and we exclusively licensed 30 pending patent applications under the OUI/MRC License that cover compositions of matter and methods of use, including applications in Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, Mexico, the Russian Federation, Saudi Arabia, and the U.S. Any patents issuing from these patent applications would expire in 2039 to 2045, without accounting for any available patent term adjustments or extensions.

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With respect to our EDO platform, we owned one pending PCT international patent application and exclusively licensed one issued European patent (validated in France, Germany, Italy, Spain, and Great Britain) and 42 pending patent applications under the OUI/MRC License that cover compositions of matter and methods of use, including applications in Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, Mexico, the Russian Federation, Saudi Arabia, and the U.S. The issued European patent is expected to expire in 2035, without accounting for any available patent term adjustments or extensions. The issued European patent was validated in France, Germany, Italy, Spain, and Great Britain, and it relates to certain compositions of matter and uses that may be utilized during future platform development activities. Any patents issuing from the patent applications would have expiration dates ranging from 2035 to 2043, without accounting for any available patent term adjustments or extensions.

Government Regulation

The FDA and comparable regulatory authorities in state and local jurisdictions and in other countries impose requirements upon companies involved in the clinical development, manufacture, marketing and distribution of drugs, such as those we are developing. These agencies and other federal, state and local entities regulate, among other things, the research and development, testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling and export and import of drugs.

U.S. Government Regulation of Drug Products

In the U.S., the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, such as the FDA’s refusal to approve pending New Drug Applications, or NDAs, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

The process required by the FDA before a drug may be marketed in the U.S. generally involves the following:

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Completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s GLP regulations;

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Submission to the FDA of an IND, which must become effective before human clinical trials may begin;

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Approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated;

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Performance of adequate and well-controlled human clinical trials in accordance with Good Clinical Practice, or GCP, requirements to establish the safety and efficacy of the proposed drug product for each proposed indication;

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Submission to the FDA of an NDA after completion of all pivotal trials, together with the payment of application user fees, as applicable;

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A determination by the FDA within 60 days of its receipt of an NDA to accept the marketing application for review;

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Satisfactory completion of an FDA advisory committee review, if applicable;

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Satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

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Satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data; and

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FDA review and approval of the NDA.

Preclinical Studies

Before testing any drug product candidate, including our product candidates, in humans, the product candidate must undergo rigorous preclinical testing. Preclinical studies include laboratory evaluation of product chemistry, toxicity and formulation, as well as in vitro and animal studies to assess potential safety and efficacy. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP regulations for safety/toxicology studies.

Prior to beginning the first clinical trial with a product candidate in the U.S., we must submit an IND to the FDA. An IND sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or literature and plans for clinical studies, among other things, to the FDA as part of an IND. An IND is a request for authorization from the FDA to administer an investigational product to humans and must become effective before human clinical trials may begin. Some preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue even after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinical trials and places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to initiate.

Clinical Trials

Clinical trials involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators in accordance with GCP requirements, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other

things, the objectives of the trial, the parameters to be used in monitoring safety, and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, an IRB representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it is initiated at that institution. An IRB is charged with protecting the welfare and rights of trial participants and considers such items as whether the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also must review and approve the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the clinical trial until completion.

Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a DSMB, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Information about certain clinical trials must be submitted within specific timeframes to the National Institutes of Health, or NIH, for public dissemination on their www.clinicaltrials.gov website. Information related to the product, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is made public as part of the registration of the clinical trial. Although sponsors are obligated to disclose the results of their clinical trials after completion, disclosure of the results can be delayed in some cases for some time. Failure to timely register a covered clinical study or to submit study results as provided for in the law can give rise to civil monetary penalties and also prevent the non-compliant party from receiving future grant funds from the federal government.

Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined:

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Phase 1: The drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness.

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Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

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Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and to provide adequate information for the labeling of the product. Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of an NDA.

Post-approval trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval on an NDA.

Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more frequently if SAEs occur. Written IND safety reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human subjects and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure. The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting. The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

NDA Submission and FDA Review and Approval

Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and proposed labeling, among other things, are submitted to the FDA as part of an NDA requesting approval to market the product for one or more indications. Data may come from company-sponsored clinical trials intended to test the safety and effectiveness of a use of a product, or from a number of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and effectiveness of the investigational drug product for the proposed indication to the satisfaction of the FDA. In most cases, the submission of an NDA is subject to a substantial application user fee; a waiver of such fees may be obtained under certain limited circumstances.

The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective

and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA, for a new molecular entity to review and act on the submission, and six months from the filing date of a new molecular entity NDA with priority review. Accordingly, this review process typically takes 12 months and eight months, respectively from the date the NDA is submitted to the FDA. The FDA does not always meet its PDUFA goal dates for standard or priority NDAs, and the review process is often extended by FDA requests for additional information or clarification. The FDA reviews an NDA to determine, among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed, packaged or held meets standards designed to assure the product’s continued safety, quality and purity.

In addition, under the Pediatric Research Equity Act of 2003, or PREA, as amended, certain NDAs or supplements to an NDA must contain data that are adequate to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. A sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration must submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before initiation of the Phase 3 or Phase 2/3 study. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from pediatric studies along with supporting information. The FDA and the sponsor must reach an agreement on the PSP. A sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based on data collected from preclinical studies, early phase clinical trials and/or other clinical development programs.

The FDA may refer an application for a novel drug or a drug that presents difficult questions of safety or efficacy to an advisory committee. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, which reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

The FDA also may require the submission of a Risk Evaluation and Mitigation Strategy, or REMS, if it determines that a REMS is necessary to ensure that the benefits of the drug outweigh its risks and to assure the safe use of the drug. A REMS may include one or more elements, including medication guides, physician communication plans, patient package insert and/or elements to assure safe use, such as restricted distribution methods, patient registries or other risk minimization tools. The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the NDA without a REMS, if required.

Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements.

After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in some cases, a Complete Response Letter. A Complete Response Letter indicates that the review cycle of the application is complete, and the application will not be approved in its present form. A Complete Response Letter generally outlines the deficiencies in the submission and contains a statement of specific conditions that must be met in order to secure final approval of the NDA; it may require additional clinical or preclinical testing in order for FDA to reconsider the application. If a Complete Response Letter is issued, the applicant may either resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. If and when those conditions have been met to the FDA’s satisfaction, the FDA will typically issue an approval letter. An approval letter authorizes commercial marketing of the drug with specific prescribing information for specific indications.

Even if the FDA approves a product, it may limit the approved indications for use of the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS, which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs. After approval, some types of changes to the approved product, such as adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements and FDA review and approval.

Orphan Drug Designation and Exclusivity

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug product intended to treat a rare disease or condition, which is generally a disease or condition that affects either (i) fewer than 200,000 individuals in the U.S., or (ii) more than 200,000 individuals in the U.S. and for which there is no reasonable expectation that the cost of developing and making the product

available in the U.S. for this type of disease or condition will be recovered from sales of the product. A company must request orphan drug designation before submitting an NDA. If the request is granted, the FDA will disclose the identity of the therapeutic agent and its potential use. Orphan drug designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product with orphan status receives the first FDA approval for the disease or condition for which it has such designation or for a select indication or use within the rare disease or condition for which it was designated, the product is entitled to orphan product exclusivity. Orphan product exclusivity means that the FDA may not approve any other applications to market the same product for the same indication for seven years, except in certain limited circumstances. Orphan exclusivity will not bar approval of another product under certain circumstances, including if a subsequent product with the same active ingredient for the same indication is shown to be clinically superior to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with orphan drug exclusivity is not able to meet market demand. Further, the FDA may approve more than one product for the same orphan indication or disease as long as the products contain different active ingredients. Moreover, competitors may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan drug has exclusivity. Other benefits of orphan drug designation include tax credits for certain research and waiver from the NDA application fee.

A designated orphan drug many not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation. In addition, orphan drug exclusive marketing rights in the U.S. may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if a second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Expedited Development and Review Programs

The FDA maintains several programs intended to facilitate and expedite development and review of new drugs to address unmet medical needs in the treatment of serious or life-threatening diseases or conditions. These programs include Fast Track designation, Breakthrough Therapy designation, Priority Review and Accelerated Approval, and the purpose of these programs is to either expedite the development or review of important new drugs to get them to patients earlier than under standard FDA development and review procedures.

The FDA has a Fast Track designation program that is intended to expedite or facilitate the process for reviewing new drugs that meet certain criteria. Specifically, new drugs are eligible for Fast Track designation if they are intended to treat a serious or life threatening condition and preclinical or clinical data demonstrate the potential to address unmet medical needs for the condition. Fast Track designation applies to both the product and the specific indication for which it is being studied. The sponsor can request that the FDA grant the product Fast Track designation any time before receiving NDA approval, but ideally no later than the pre-NDA meeting. Fast Track designation provides increased opportunities for sponsor interactions with the FDA review team to expedite development and review of the product. The FDA may also review sections of the NDA for a Fast Track designated-product on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the application, the FDA agrees to accept sections of the application and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the application. Fast Track designation may be lost if the designation is no longer supported by data emerging in the clinical trial process.

Additionally, a drug may be eligible for designation as a breakthrough therapy if the product is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life- threatening condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over currently approved therapies on one or more clinically significant endpoints. The benefits of Breakthrough Therapy designation include the same benefits as Fast Track designation, plus intensive guidance from the FDA to ensure an efficient drug development program. Breakthrough therapy designation comes with all of the benefits of Fast Track designation, which means that the sponsor may file sections of the NDA for review on a rolling basis if certain conditions are satisfied, including an agreement with the FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review.

A product may also be eligible for priority review if it treats a serious or life-threatening condition and, if approved, would provide a significant improvement in safety and effectiveness compared to available therapies. The FDA determines at the time that the marketing application is submitted, on a case-by-case basis, whether the proposed drug represents a significant improvement in treatment, prevention or diagnosis of disease when compared with other available therapies. A priority review designation is intended to direct overall attention and resources to the evaluation of such applications and to shorten the FDA’s goal for taking action on a marketing application from ten months to six months for an NDA for a new molecular entity from the date of filing. If criteria are not met for priority review, the application for a new molecular entity is subject to the standard FDA review period of ten months after FDA accepts the application for filing. Priority review designation does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

A product may also be eligible for accelerated approval if it treats a serious or life-threatening disease or condition, generally provides a meaningful advantage over available therapies and demonstrates an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, or IMM, that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments. As a condition of accelerated approval, the FDA generally requires that a sponsor perform adequate and well-controlled post-marketing clinical trials to verify and describe the product’s clinical benefit. These confirmatory trials must be completed with due diligence, and, under the Food and Drug Omnibus Reform Act of 2022, or

FDORA, the FDA is now permitted to require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted accelerated approval. Under FDORA, the FDA has increased authority for expedited procedures to withdraw the product from the market (and withdraw its approval). In addition, for products being considered for accelerated approval, the FDA generally requires, unless otherwise informed by the agency, pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened. Fast Track designation, Breakthrough Therapy designation, priority review and accelerated approval do not change the standards for approval and may not ultimately expedite the development or approval process.

U.S. Non-Patent Exclusivity

Market exclusivity provisions under the FDCA can delay the submission or the approval of certain follow-on applications. The FDCA provides a five-year period of data exclusivity within the U.S. to the first applicant to gain approval of an NDA for a new chemical entity, or NCE. A drug is a NCE if the FDA has not previously approved any other new drug containing the same active moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not accept for review an Abbreviated New Drug Application, or ANDA, for a generic version of the drug or a 505(b)(2) NDA for another version of such drug where the applicant does not own or have a legal right of reference to all the data required for approval. However, such a follow-on application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder.

The FDCA also provides three years of market exclusivity for an NDA, 505(b)(2) NDA or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, new indications, dosages or strengths of an existing drug. This three-year exclusivity period covers only the conditions of use associated with the new clinical investigations and does not prohibit the FDA from approving follow-on applications that do not reference the protected clinical data. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

PEPG US Equity

PEPG · 10-K · period ended 2024-12-31

Item 1. Business.

PEPG US Equity☆

PEPG · 10-K · period ended 2024-12-31

Item 1. Business.

PEPG US Equity