10-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 10-K

(Mark One)

For the fiscal year ended December 31, 2022

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 March 15, 2023, was $114.2 million. The number of shares of Registrant’s Common Stock outstanding as of March 15, 2023 was 23,781,905.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the registrant’s Definitive Proxy Statement relating to its 2023 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 60

Item 1B. Unresolved Staff Comments 120

Item 2. Properties 120

Item 3. Legal Proceedings 120

Item 4. Mine Safety Disclosures 120

PART II

Item 6. [Reserved] 121

Item 7A. Quantitative and Qualitative Disclosures About Market Risk 130

Item 8. Financial Statements and Supplementary Data 130

Item 9A. Controls and Procedures 130

Item 9B. Other Information 131

Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 133

PART III

Item 10. Directors, Executive Officers and Corporate Governance 134

Item 11. Executive Compensation 134

Item 14. Principal Accounting Fees and Services 134

PART IV

Item 15. Exhibits, Financial Statement Schedules 135

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 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 and foreign countries;

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our ability to contract with third-party suppliers and manufacturers and their ability to perform adequately;

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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 effect of the ongoing COVID-19 pandemic, 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 Securities and Exchange Commission 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 Annual Report on Form 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 very early in our development efforts. We have only advanced one product candidate into clinical development, 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 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 those of the Phase 1 study of PGN-EDO51, are not necessarily predictive of the results of later preclinical studies and any clinical trials of our product candidates. We have only entered clinical trials for one of our product candidates and 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 planned clinical trials or failure to demonstrate safety and efficacy to the satisfaction of applicable regulatory authorities could prevent us from commercializing any 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 and preclinical and clinical testing, and these third parties may not perform satisfactorily or, dedicate adequate resources to meet our needs, or may be unable to acquire the necessary supplies to perform successfully.

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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 EDO 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 development and regulatory 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 may be volatile and fluctuate 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 Annual Report on Form 10-K, as well as in other documents that we file with the U.S. Securities and Exchange Commission (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

We are 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 Enhanced Delivery Oligonucleotide, or EDO, platform is founded on over a decade of research and development and leverages cell-penetrating peptides to improve the uptake and activity of conjugated oligonucleotide therapeutics. This technology was initially developed through a collaboration between researchers at the University of Oxford and the Medical Research Council of United Kingdom Research and Innovation. We have in-licensed an extensive patent portfolio from these institutions to support the further advancement and potential commercialization of our EDO platform. 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 and the central nervous system, or CNS. Furthermore, the high levels of pharmacological activity observed in preclinical studies support our belief that our EDO platform technology has the potential to deliver therapeutic agents to the cell nucleus. Using these EDO peptides, we are generating a pipeline of oligonucleotide therapeutic candidates that target the root cause of serious diseases.

We are currently in clinical-stage development and completed a first-in-human Phase 1 clinical trial in healthy volunteers, or HV, with our lead product candidate, PGN-EDO51, in the third quarter of 2022. We are developing PGN-EDO51 to treat individuals with Duchenne muscular dystrophy, or DMD, whose mutations are amenable to an exon 51-skipping therapeutic approach. An exon is a segment of a gene that – together with other exons – contains the code that is translated into a protein. Exon skipping is a therapeutic modality that enables mutations in the gene to be bypassed, thereby repairing this code and enabling production of a truncated, yet functional version of the target protein. In a Phase 1 clinical trial, treatment with PGN-EDO51 resulted in the highest levels of exon skipping and oligonucleotide delivery in humans following a single dose when compared to publicly available data for other approaches. PGN-EDO51 was found to be generally well-tolerated at pharmacologically relevant dose levels in this study. In non-human primate, or NHP, studies, PGN-EDO51 at a dose of 30 mg/kg achieved over 70% exon 51 skipping in skeletal muscle, including diaphragm, and in mdx mouse studies, dystrophin levels of over 80% were observed in skeletal muscle following a single 60 mg/kg dose of PGN-EDO23, the murine analogue of PGN-EDO51. These results represent what we believe to be the highest level of exon 51 skipping in NHP skeletal muscle at tolerable target dose levels, and the highest level of dystrophin production in mdx mouse skeletal muscle when compared to other clinical-stage DMD therapeutic candidates. In addition, in head-to-head NHP studies, we observed that PGN-EDO51 had greater activity than R6G-PMO, which we believe to be structurally equivalent to Sarepta Therapeutics, Inc.’s, or Sarepta’s, SRP-5051, the most clinically advanced peptide-ASO conjugate. Moving forward, our clinical development program comprises two, parallel Phase 2 studies of PGN-EDO51 in DMD patients whose disease is amenable to an exon 51 skipping approach. The first study, CONNECT1-EDO51, is expected to be an open-label, multiple ascending dose, or MAD, study to open in Canada in the first half of 2023, with initial dystrophin, exon skipping and safety data anticipated in 2024. The second study, CONNECT2-EDO51, is expected to be a global, randomized, double-blind, placebo-controlled MAD clinical trial, or RCT, anticipated to open in the second half of 2023, pending clearance by the U.S. Food and Drug Administration, or FDA, of an Investigational New Drug, or IND filing, and/or clearance by the European Medicines Agency of a Clinical Trial Application, or CTA, in each case, anticipated in the second half of this year. Learnings from the open-label Phase 2 study will inform the conduct of the global RCT which is intended to support a potential accelerated approval pathway for PGN-EDO51. Building on the high levels of exon skipping and tissue concentration observed in our Phase 1 trial, we believe that repeat dosing of PGN-EDO51 may lead to the accumulation of exon 51 skipped transcript and dystrophin protein in patients, which may in turn drive meaningful clinical benefit for those who live with this devastating, progressive, life-shortening disease.

We are also developing PGN-EDODM1 for the treatment of myotonic dystrophy type 1, or DM1, and are utilizing what we believe to be a unique mechanism of action. The therapeutic oligonucleotide component of PGN-EDODM1 is engineered to bind to the cytosine-uracil-guanine (CUG) repeat expansion present in the DMPK mRNA of DM1 patients, thus potentially reducing the ability of these trinucleotide repeats to sequester MBNL1, a critical transcription factor. The liberation of MBNL1 in turn leads to the correction of downstream mis-splicing events that are evident in DM1, and thus we believe this approach – which is not designed to knock down DPMK – is intended to directly addresses the underlying genetic defect of this disease. Treatment with PGN-EDODM1 resulted in the robust correction of mis-splicing in preclinical models with both long and short CTG repeats, including in the HSALR mouse model, where complete reversal of myotonia was also observed following a single dose. Furthermore, the oligonucleotide concentrations that were observed to be pharmacologically active in this mouse model of DM1 were found to be comparable to the tissue concentrations of oligonucleotide in human muscle observed in our clinical trial of PGN-EDO51. We expect to open our FREEDOM-DM1 Phase 1 randomized, placebo-controlled single ascending dose, or SAD, clinical trial of PGN-EDODM1, in DM1 patients in the first half of 2023, with functional assessments, correction of mis-splicing and safety data anticipated in 2024. Based on data obtained in our Phase 1 HV study of PGN-EDO51, we believe that PGN-EDODM1 has the potential to achieve tissue concentrations in people living with DM1 that could lead to clinically meaningful outcomes.

In addition to these lead candidates, we are developing EDO therapeutics for further DMD exon skipping populations, including exon 53-, 45- and exon 44-skipping amenable patients, and have observed robust exon skipping levels in NHP for our PGN-EDO53 program, and in wild-type human cells for our PGN-EDO45 and PGN-EDO44 programs. We have also initiated research efforts for additional indications, including neuromuscular diseases and neurologic disorders, and from this pipeline of candidates we anticipate advancing additional programs into clinical trial application, or CTA and investigational new drug, or IND-enabling studies in 2024.

The advent of oligonucleotide therapeutics represented a major advance in the history of the biopharmaceutical industry. Oligonucleotide therapeutics are a nucleic acid-based genetic medicine modality that is designed to target the root cause of many diseases through the modulation of RNA expression and processing. These therapeutics have demonstrated clinical benefit and been approved for the treatment of multiple diseases. The approved drugs within this category include antisense oligonucleotides, or ASOs, which are short, synthetic, single-stranded oligonucleotides designed to inhibit or modify expression of protein and RNA.

However, despite the considerable potential of oligonucleotides as a therapeutic class, the challenges associated with their delivery has limited the development of these therapies in certain disease areas. On their own, oligonucleotides therapeutics are not readily distributed to heart and skeletal muscle, the key tissues affected in neuromuscular diseases, and are not efficiently taken up into these cells.

Our EDO Platform

To address this challenge, we engineered our proprietary EDO technology to optimize tissue penetration, cellular uptake and nuclear delivery, which we believe may enhance the therapeutic activity of oligonucleotides and improve the tolerability of these genetic medicines. Our platform is based on novel cell-penetrating EDO peptides that were developed through an iterative process which selected simultaneously for high cellular uptake, biodistribution to key muscle targets, including cardiac tissue, and improved tolerability. We utilize phosphorodiamidate morpholino oligomers, or PMOs, a type of ASO chemistry that confers enhanced stability, 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. We are continuing to build and develop this platform technology as we expand into new therapeutic areas.

Using this novel, proprietary platform, we are developing a broad pipeline of disease-modifying EDO candidates to treat a variety of degenerative neuromuscular and neurologic diseases. Our platform is designed to offer the following advantages compared to existing oligonucleotide approaches:

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Enhanced delivery to skeletal muscle, including diaphragm, cardiac muscle and the CNS.

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Improved activity, which we have observed in a clinical trial and in preclinical studies:

In healthy volunteers, we observed the highest levels of exon skipping and oligonucleotide delivery in humans following a single dose of PGN-EDO51 when compared to publicly available data for other exon 51 skipping approaches;

In NHPs, we observed what we believe to be the highest rate of exon 51 skipping in skeletal muscles, including the diaphragm, at tolerable target dose levels of PGN-EDO51 compared to the reported data for any approved therapeutic or known developmental candidate;

In the mdx mouse model, we observed the highest level of dystrophin production in skeletal muscle following a single dose of PGN-EDO23, the murine analogue of PGN-EDO51, when compared to what has been reported for clinical-stage DMD therapeutic candidates.

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An enhanced balance between activity and tolerability, which is designed to afford our product candidates a wider therapeutic index.

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Robust, scalable and cost-efficient manufacturing that does not require cell-based processes.

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Accelerated and efficient pipeline development of therapeutic candidates enabled by use of the same EDO peptide across all our initial programs.

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 and to exhibit a favorable tolerability profile. 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 five programs. We anticipate expanding this pipeline to include other neuromuscular targets as well as opportunities in neurologic indications and intend to leverage the modular, scalable nature of our EDO technology to support our expansion into these new therapeutic areas. Our lead product candidates, PGN-EDO51 and PGN-EDODM1, target a large potential market opportunity, with approximately 135,000 DMD exon 51

and DM1 patients across the United States, Europe and Japan, and we own worldwide development and commercialization rights to all our programs.

PGN-EDO51

Our lead product candidate is PGN-EDO51, an EDO peptide conjugated to a PMO therapeutic cargo, which we are developing for the treatment of DMD patients with mutations amenable to an exon 51-skipping approach. DMD is a debilitating X-linked recessive muscle-wasting disease that predominantly affects boys, and arises due to the presence of mutations in the gene encoding dystrophin, a protein necessary for normal muscle function. It is one of the most prevalent rare genetic diseases globally, with up to 15,000 DMD patients in the United States, approximately 25,000 DMD patients in Europe and 5,000 in Japan. It is thought that 13% of patients with DMD have mutations that are amenable to treatment with an exon 51-skipping therapeutic approach, and thus the estimated exon 51 patient population is approximately 2,000 in the United States, 3,200 in Europe and 700 in Japan. DMD patients typically succumb to cardiac and respiratory failure in their early adulthood with a mean lifespan of approximately 25 years. There is no cure for DMD and there are no treatments that have clinically demonstrated a meaningful impact on disease progression.

PGN-EDO51 is designed to splice out exon 51 of the dystrophin pre-mRNA, resulting in the restoration of the open reading frame of the dystrophin transcript and the production of a shortened, yet functional dystrophin protein. In a Phase 1 clinical trial of PGN-EDO51, we observed the highest levels of exon skipping and oligonucleotide concentration in muscle in humans following a single dose, when compared to publicly available data for other exon 51 skipping approaches. In wild-type NHP studies, at tolerable doses, we have observed what we believe is the highest rate of exon 51 skipping in skeletal muscle, including diaphragm, based on cross-trial comparisons with publicly available data for any approved therapeutic or known developmental candidate. These cross-trial comparisons were conducted with data published by Sarepta for EXONDYS 51® (eteplirsen), and by Dyne Therapeutics, Inc, or Dyne for DYNE-251. In addition, in head-to-head NHP studies, we observed that PGN-EDO51 had greater activity than R6G-PMO at the same dose level, a comparator compound that we believe to be structurally equivalent to Sarepta’s SRP-5051, the most clinically advanced peptide-ASO conjugate. At a dose of 10 mg/kg, PGN-EDO51 exhibited approximately as much exon skipping activity as a 3-fold higher dose, i.e., 30 mg/kg, of R6G-PMO. In the mdx mouse model, we observed the highest level of dystrophin production in skeletal muscle following a single dose of PGN-EDO23, the murine analogue of PGN-EDO51, when compared to other clinical-stage DMD therapeutic candidates. Our Phase 1 clinical trial also indicated that PGN-EDO51 was generally well-tolerated at pharmacologically relevant dose levels. In 2023, we anticipate opening two clinical trials in DMD patients amenable to an exon 51 skipping approach. CONNECT1-EDO51 is an open-label MAD study to open in Canada in the first half of 2023, with initial dystrophin, exon skipping and safety data anticipated in 2024. CONNECT2-EDO51 is a multinational, randomized, placebo-controlled MAD clinical trial anticipated to open in the second half of 2023, and is designed to potentially support a future potential accelerated approval pathway.

PGN-EDODM1

We are developing PGN-EDODM1, an EDO peptide-conjugated PMO, for the treatment of DM1. DM1 is a monogenic, autosomal dominant, progressive disorder that primarily affects skeletal, cardiac and smooth muscles as well as the CNS, resulting in significant physical, cognitive and behavioral impairments and disability. The burden of disease is significant, and many patients have

a shortened lifespan. DM1 is caused by an abnormal trinucleotide repeat expansion in a region of the DMPK gene and is estimated to affect approximately 40,000 patients in the United States, 75,000 patients in Europe and 15,000 patients in Japan. There are currently no approved therapies for the treatment of DM1.

PGN-EDODM1 leverages the same EDO peptide as PGN-EDO51 to deliver a PMO into muscle cells that binds to the cytosine-uracil-guanine, or CUG, trinucleotide repeat expansion present in the DMPK mRNA, thus reducing the ability of these trinucleotide repeats to sequester MBNL1, a critical RNA processing protein. This approach – which is not designed to knock down DPMK – 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 ex vivo, we observed that treatment with PGN-EDODM1 led to the robust correction of multiple downstream mis-spliced transcripts and a reduction in toxic nuclear foci. In our in vivo preclinical studies, a single dose of PGN-EDODM1 was observed to correct the molecular and functional phenotypes presented in the human skeletal actin – long repeat, or HSALR, mouse model of disease, ameliorating downstream mis-splicing events, reversing myotonia and normalizing mobility. We also observed that the molecular correction effected by PGN-EDODM1 in this preclinical mouse model exhibited a durability of effect that was in excess of six months. Furthermore, the tissue concentrations of oligonucleotide that were found to be pharmacologically active in the HSALR mouse model were similar to those observed for PGN-EDO51 in human muscle in a Phase 1 study, supporting our belief in the ability of PGN-EDODM1 to achieve potentially safe and effective therapeutic levels of oligonucleotide in the clinic. We expect to open our FREEDOM-DM1 Phase 1, randomized, placebo-controlled SAD clinical trial of PGN-EDODM1 in DM1 patients in the first half of 2023, with functional assessments, correction of mis-splicing and safety data anticipated in 2024.

Additional DMD Programs

We are developing additional EDO therapeutics for further DMD patient populations, including PGN-EDO53, for the 8% of DMD patients who are amenable to an exon 53-skipping approach, PGN-EDO45, for the 8% of DMD patients who are amenable to an exon 45-skipping approach, and PGN-EDO44, for the 6% of DMD patients who are amenable to an exon 44-skipping approach. These programs utilize the same EDO cell penetrating peptide as our exon 51-skipping product candidate, PGN-EDO51, which we believe will allow us to leverage our drug development experience with this peptide, and in this indication, to rapidly drive our exon 53, 45 and 44-skipping product candidates forward. In a NHP study of PGN-EDO53, we observed single-dose exon skipping levels that were almost seven times higher than those observed for R6G-PMO53, a relevant comparator peptide-PMO conjugate approach. For PGN-EDO45, high, dose-dependent levels of exon skipping were observed in wild-type human myoblasts, with our nominated candidate outperforming the R6G-PMO45 comparator at every dose level assessed. Finally, our PGN-EDO44 nominated candidate also exhibited high, dose-dependent levels of exon skipping in wild-type human myoblasts. We anticipate providing further updates on these programs as preclinical development continues.

Expanding the Applications and Scope of Our EDO Platform

New indications with PMO therapeutics

We intend to leverage our deep understanding of our EDO platform and oligonucleotide therapeutic candidates to develop additional product candidates for other indications. We believe the ability of our EDO technology to deliver exon skipping therapeutics to muscle cells, including cardiac muscle cells, as well as the CNS is largely independent of the exact sequence of the PMO. As such, by leveraging our preclinical data and the plug-and-play nature of our EDO platform, we believe that we are well positioned to develop additional product candidates with the potential to drive clinically relevant therapeutic outcomes in other neuromuscular diseases as well as neurologic indications.

New cargos

We believe that our EDO technology has the potential to facilitate the delivery of multiple classes of oligonucleotide therapeutics. To date, our efforts have primarily focused on the delivery of PMOs, but we are also actively pursuing 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 cell penetrating peptides. We will leverage our extensive experience in this field to design new peptides that target specific tissue types, and will seek to further optimize the tissue, cellular and nuclear delivery of our EDO platform technology.

Our Culture and Team

Our mission is to deliver transformative therapeutics to those in need, and we believe our innovative technology is well-positioned to effect this change for patients, families and the broader healthcare community. As a company, we value:

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Research: We are a data-driven scientific company at heart, and we approach our work with an evidence-based mindset;

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Innovation: We are always exploring new ways to learn, build and improve across all facets of our company;

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Integrity: We act ethically and honestly in both our scientific and business conduct; and

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Responsibility: As a therapeutic company, we appreciate the impact our work has on patients and their families.

In support of our mission, we have assembled a leadership team with deep experience in research and development, clinical translation, regulatory affairs and corporate development. Our Chief Executive Officer, James McArthur, Ph.D., brings over 25 years of industry experience to the company, including senior leadership and Board roles at Imara Inc., Cydan LLC and Nightstar Therapeutics plc, with a specific focus on rare disease therapeutics. Dr. McArthur is ably supported by Noel Donnelly, M.B.A., our Chief Financial Officer, who has over 25 years of experience in financial planning and analysis, business analytics and portfolio management and has held roles at EIP Pharma Inc., Takeda Pharmaceuticals, Inc., and Shire HGT; Jaya Goyal, Ph.D., our Executive Vice President of Research and Preclinical Development, who has held roles at Wave Life Sciences Ltd., and Biogen Inc., and brings considerable experience in bioanalytical studies, biomarkers and pharmacology across a broad range of preclinical-, clinical- and commercial-stage programs; Michelle L. Mellion, M.D., our Senior Vice President, Clinical Development, who is double Board-certified in neurology and clinical neurophysiology and has held roles at Fulcrum Therapeutics, Inc., Vertex Pharmaceuticals, Inc., and Biogen Inc; Niels Svenstrup, Ph.D., our Senior Vice President of Chemistry, Manufacturing and Control, who has extensive experience in the manufacturing and release of peptide drugs for late-stage clinical programs and has held roles at Ascendis Pharma A/S, Cydan LLC, and Lundbeck A/S, amongst others. We have established a strong scientific advisory board, who bring a wealth of expertise from both the indication and therapeutic modality perspectives in their roles as academics, clinicians and drug developers.

We were founded in 2018 with technology spun out from the University of Oxford and the Medical Research Council of United Kingdom Research and Innovation to further develop and commercialize this novel peptide delivery approach. This technology was created and refined over a decade by Michael Gait, Ph.D. and Professor Matthew Wood, M.D., Ph.D. We have exclusively licensed the patents, patent applications and know-how associated with this technology.

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 our lead product candidate, PGN-EDO51, through clinical trials and potential regulatory approval. We are developing PGN-EDO51 to treat individuals with DMD whose mutations are amenable to an exon 51-skipping therapeutic approach. There is no cure for DMD and there are no treatments that have demonstrated a significant impact on disease progression in the clinic. In a Phase 1 clinical trial of PGN-EDO51, we observed the highest levels of exon skipping and oligonucleotide delivery to muscle in humans following a single dose when compared to publicly available data for other exon 51 skipping approaches. In wild-type NHP studies, we observed what we believe to be the highest rate of exon 51 skipping in skeletal muscle, including the diaphragm, at tolerable target dose levels when compared to any approved therapeutic or known developmental candidate, and in mdx mice we observed the highest level of dystrophin production in skeletal muscle following a single dose when compared to such data reported for other clinical-stage DMD candidates. Furthermore, in a head-to-head study conducted in NHP, we observed that PGN-EDO51 had greater activity than R6G-PMO at the same clinically-relevant dose level, a comparator compound that we believe to be structurally equivalent to Sarepta’s SRP-5051, the most clinically advanced peptide-ASO conjugate. In our Phase 1 clinical trial, we also observed that PGN-EDO51 was generally well-tolerated at pharmacologically relevant dose levels. In 2023, we anticipate opening two clinical trials in DMD patients amenable to an exon 51 skipping. CONNECT1-EDO51 is an open-label MAD study to open in Canada in the first half of 2023, with initial dystrophin, exon skipping and safety data anticipated in 2024. CONNECT2-EDO51 is a multinational, randomized, placebo-controlled MAD clinical trial anticipated to open in the second half of 2023, and is designed to potentially support a future accelerated approval pathway.

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Advance PGN-EDODM1 through clinical trials and potential regulatory approval. We are developing PGN-EDODM1 for the treatment of patients with DM1, and have observed robust pharmacological activity in preclinical models with both long and short CTG repeats. In a mouse model of DM1 we have observed that a single dose of PGN-EDODM1 corrected mis-splicing resulting in resolution of myotonia and improved mobility that was maintained for at least six months. The tissue concentrations of oligonucleotide that were found to be pharmacologically active in the HSALR mouse model were similar to those observed for PGN-EDO51 in human muscle in a Phase 1 study, supporting the ability of PGN-EDODM1 to achieve potentially therapeutic levels of oligonucleotide in the clinic. We believe that PGN-EDODM1 has the potential to

transform the treatment of DM1, and we expect to open our FREEDOM-DM1 Phase 1, randomized, placebo-controlled SAD clinical trial of PGN-EDODM1 in DM1 patients in the first half of 2023. Functional assessments, correction of mis-splicing and safety data from this trial are anticipated in 2024. Furthermore, we believe that the successful development of PGN-EDODM1 would further support the EDO platform and demonstrate its potential to generate therapeutic candidates in neuromuscular indications beyond DMD.

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Expand our pipeline of oligonucleotide therapeutic candidates for the treatment of additional DMD patient populations. We aim to expand our portfolio by pursuing additional programs where our EDO technology could improve clinical activity relative to current therapeutic approaches and address areas of great unmet need. For example, approximately one third of the mutations that cause DMD could be treated by exon-skipping therapeutics directed against exons 51, 53, 45 and 44. We are employing the same EDO technology used in PGN-EDO51 and PGN-EDODM1 for PGN-EDO53, PGN-EDO45 and PGN-EDO44, our exon-skipping therapeutic candidates for the treatment of individuals with DMD whose mutations are amenable to treatment with exon 53-, 45- and 44-skipping approaches respectively. We have observed high levels of exon skipping in NHP for PGN-EDO53, and in wild-type human cells for PGN-EDO45 and PGN-EDO44, and anticipate providing further updates on these programs as development progresses.

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Leverage the full potential of our EDO technology to expand into other neuromuscular, neurological and cardiac disease areas. We have observed both clinically and preclinically that our EDO technology has the potential to efficiently deliver nucleic acid payloads such as ASOs to muscle cells, including cardiac muscle cells, and into key regions of the brain in NHP. We are looking to develop disease-modifying peptide-conjugated oligonucleotide candidates for the potential treatment of a variety of other neuromuscular and neurological indications and will assess alternative routes of administration, including intrathecal, as part of this process.

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Utilize the modular nature of our EDO platform to evaluate new cargos and peptide technologies. We continue to optimize our EDO technology to increase our ability to drive the biodistribution of our conjugates to desired target tissues in the body. To accomplish this, we have built and continue to build our peptide chemistry and biology groups to further explore the structure-activity relationship of our existing EDO platform and to develop new delivery peptides. These next-generation peptides may allow us to develop potential disease-modifying therapeutic candidates for an expanded range of target indications. Furthermore, 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 we will thus seek 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; to the advancement of our programs in maximizing their market potential; or to the expansion of our platform capabilities.

Our EDO Platform

Overview

Our proprietary EDO platform is based on a novel, unique class of cell-penetrating peptides, or CPPs, that were designed to meaningfully enhance the tissue penetration, cellular uptake and nuclear delivery of oligonucleotide therapeutics. This technology is founded on over a decade of research and development that focused on improving the therapeutic utility of CPPs, resulting in a library of EDO peptides that mitigate the tolerability challenges observed with earlier cell-penetrating peptides. Using these EDO peptides, we are generating a pipeline of peptide-conjugated oligonucleotide therapeutic candidates that are engineered to successfully target the root cause of serious diseases and to exhibit a favorable tolerability profile. We believe that our approach to oligonucleotide delivery is potentially best-in-class, a belief that is supported by our observation of the highest levels of exon skipping and oligonucleotide delivery in humans following a single dose of PGN-EDO51 when compared to publicly available data for other exon 51 skipping approaches, and a generally well-tolerated profile for this product candidate observed, to date, at pharmacologically relevant dose levels. In wild-type NHP studies, we observed what we believe to be the highest rate of exon 51 skipping in skeletal muscle, including the diaphragm, at tolerable target dose levels compared to any approved therapeutic or known developmental candidate, and in mdx mice we observed the highest level of dystrophin production in skeletal muscle following a single dose when compared to other clinical-stage DMD candidates. For these human, NHP, and murine studies, such comparisons were conducted both across different trials with publicly available information, and in some instances with data obtained from head-to-head studies, and encompass unconjugated, peptide-conjugated, antigen binding fragment-conjugated and monoclonal antibody-conjugated oligonucleotide therapeutic approaches. The totality of the clinical and preclinical datasets that underpin our EDO technology highlight the potential ability of our CPP platform to address critical disease phenotypes in neuromuscular indications like DMD and DM1, with our lead

EDO therapeutic candidates being focused on these two indications. Our peptides also enable delivery of oligonucleotides across the blood-brain barrier, a characteristic which could support the future development of EDO therapeutics for neurologic indications.

Our EDO technology is designed to address the delivery challenges that limit oligonucleotide therapeutics.

The Therapeutic Potential of Oligonucleotides

The central dogma of biology—the transcription of DNA into RNA, and the subsequent translation of RNA into proteins—describes the flow of genetic information within the cell. DNA plays a critical, fundamental role in all biological processes, and while there exists considerable variation in the genetic code across the human population, certain alterations, or mutations, in an individual’s DNA sequence can lead to deleterious outcomes and disease pathologies. A genetic disease can be caused by a mutation in a single gene, known as a monogenic disorder, or by mutations in multiple genes, known as a multifactorial inheritance disorder. The term ‘genetic medicine’ encompasses disease-modifying therapeutic agents that are designed to alter and correct genetic mutations at the DNA or RNA level. These therapeutic agents can be divided into four categories – viral vector gene therapies, DNA/RNA editing approaches, small molecules and oligonucleotide therapeutics. Significant progress has been made in the field of genetic medicine over the last decade, and a number of genetic medicines have been approved or are in clinical development.

Oligonucleotide therapeutics are a nucleic acid-based genetic medicine modality that are designed to target the root cause of many diseases 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 genes, and each of these approaches can lead to profound biological effects.

The advent of oligonucleotide therapeutics represented a major advance in the history of the biopharmaceutical industry. Oligonucleotide therapeutics consist of strings of nucleotides, the building blocks of RNA and DNA, and mimic the structures of active nucleic acids in the body to reproduce or expand upon the typical activities of these species. The development of oligonucleotide therapeutics has increased the arsenal of potential therapeutic modalities and has enabled the targeting of a diverse set of diseases that have proven difficult to treat through other approaches. These therapeutic candidates are built around the sequences of their target RNA/DNA molecules, which offers them a high degree of specificity and affords them the ability to target pathogenic mutations and processes that cannot easily be addressed by conventional drugs. Oligonucleotide therapeutics have demonstrated clinical benefit and been approved for the treatment of multiple diseases, such as spinal muscular atrophy, 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 via complementary Watson-Crick base pairing, 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 a particular mRNA through the RNA interference, or RNAi, pathway. Across approved oligonucleotide therapeutics, in 2020, approximately $3.2 billion in sales were generated.

Therapeutic oligonucleotides 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. The resulting oligonucleotides – 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 reached the clinic in a number of indications, including DMD. Sarepta’s marketed drug EXONDYS 51® (eteplirsen) is a PMO that was approved in 2016 but has left much room for improvement given its relatively low tissue and cell penetration and minimal induction of dystrophin production. Despite these challenges, EXONDYS 51® generated approximately $454 million in sales in the United States and Israel in 2021.

The Challenge of Oligonucleotide Delivery

In order for oligonucleotide therapeutics to exert their intended effect, they must first gain access to the intracellular space where RNA processing and translation occurs. 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 into 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 cell-penetrating peptides, or CPPs. CPPs are designed to facilitate the transport of oligonucleotides across the plasma membrane, thus allowing these cargo species to reach their intracellular site of action. 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

We engineered our proprietary EDO technology to optimize tissue penetration, cellular uptake and nuclear delivery, which we believe may enhance the therapeutic activity and improve the tolerability of oligonucleotide therapeutics. Our platform is based on novel cell-penetrating peptide technology, and our delivery vectors possess four 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;

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The interspersion of a specifically selected non-natural amino acid within the arginine-rich regions – these residues provide stability in the physiological environment, and confer other beneficial properties;

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A central core rich in hydrophobic residues that separates the arginine-rich regions and plays a critical role in tissue and cell uptake;

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A proprietary linker that plays a key role in modulating the therapeutic index of the resulting EDO conjugate.

Our EDO peptides were developed through an iterative optimization process that selected simultaneously for biodistribution to key muscle targets, including cardiac tissue; high cellular uptake; endosomal escape, where the therapeutic agent is released from the endosome sub-cellular compartment in a functional form; delivery to the cell nucleus; and reduced toxicity. 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. We are continuing to build and develop this platform technology as we expand into new therapeutic areas.

We optimized EDO peptides for properties that we believe are essential for therapeutics.

Advantages of Our Approach

Using our novel EDO platform, we are developing a broad pipeline of disease-modifying peptide-conjugated oligonucleotide candidates to treat a variety of degenerative neuromuscular diseases. 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 skeletal muscle, including diaphragm, cardiac muscle and the CNS: We have observed in preclinical studies that our peptides delivered their cargo oligonucleotide therapeutics to key neuromuscular tissues, allowing us to address multiple disease pathologies in multi-systemic indications such as DMD and DM1. Furthermore, we believe our EDO peptides support the ability to promote endosomal escape and facilitate the robust delivery of cargo oligonucleotides to the cell nucleus. This differentiating feature of our EDO platform has been observed in mice and NHPs across multiple tissue types, including those critical to neuromuscular indications – skeletal, smooth and cardiac muscle. We believe the ability of our EDO peptide to deliver oligonucleotides to the CNS could potentially address neurological phenotypes in these diseases as well.

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Improved activity, which we have observed in a Phase 1 clinical study, in NHPs and in mdx mice, with potentially robust levels of activity observed in skeletal muscle: Our EDO platform exhibited consistently robust activity and acceptable tolerability in a single dose clinical study conducted in healthy volunteers, and in preclinical testing in NHPs under both single and repeat dosing regimens, and in a single dose study in mdx mice. For example, in a Phase 1 clinical study of PGN-EDO51, we observed the highest levels of exon skipping and oligonucleotide delivery in humans following a single dose when compared to publicly available data for other exon 51 skipping approaches. In NHP, a dose of 30 mg/kg of PGN-EDO51 achieved over 70% exon 51 skipping in skeletal muscle, including diaphragm, which we believe is the highest rate of exon 51 skipping reported for any approved therapeutic or known development candidate at tolerable target dose levels. In mdx mice, we observed the highest level of dystrophin production following a single dose when compared to other clinical-stage DMD therapeutic candidates.

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Enhanced balance between activity and tolerability, which is designed to afford ourplatform a wider therapeutic index: Our delivery peptides have been specifically engineered to achieve a wide therapeutic index, and we have observed robust activity and an improved tolerability profile in NHPs when compared to data published on previous CPPs. In a Phase 1 clinical study, our lead EDO candidate was found to be generally well-tolerated at pharmacologically relevant dose levels. We believe this characteristic is a promising step-change over the narrow therapeutic index observed for previous generations of cell-penetrating peptides.

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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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Accelerated and 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 our programs, and we envisage that many of our future pipeline opportunities will also leverage our extensive experience with this CPP. 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.

Foundation of Our EDO Platform

A platform built on intelligent design principles and a decade of science

Our EDO peptide platform is the result of over a decade of research conducted in the academic laboratories of our founders Michael Gait, Ph.D. at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, and Professor Matthew Wood, M.D., Ph.D. at the University of Oxford. Their pioneering work brought significant advances in CPP technology, moving the field beyond a heavy reliance on arginine residues to drive cellular uptake of oligonucleotide cargos. Together, Gait and Wood developed a new generation of CPPs focused on oligonucleotide delivery, and optimized these peptides for tissue penetration, cellular uptake and nuclear delivery, along with improved tolerability in animal models.

The first generation of Gait and Wood cell-penetrating peptides were termed the ‘Pip’ series. As part of the ongoing collaboration between these two academic groups, a range of Pip-PMO conjugates were screened for their activity both in vitro and in the well-established mdx mouse model of Duchenne muscular dystrophy. While the Pips exhibited robust activity in preclinical models, they were ultimately determined to be non-viable as therapeutic candidates due to their considerable renal toxicity. However, this early work did provide considerable insight into the structure-activity relationship of this class of molecules.

The poor tolerability profile of the Pips and other early cell-penetrating peptides established a clear need for a step-change in this field. Through an intelligent design process, multiple families of ‘DPEP’ peptides were created to address the limitations associated with previous generations of CPP technology. These novel, unique peptides have overcome the tolerability issues of their predecessors and yet retain the considerable activity of the Pip peptides – a profile that we believe renders the DPEPs well-positioned for therapeutic development. The DPEP peptides underpin our EDO platform, and it is from this portfolio that we have selected and validated the EDO peptide that drives the therapeutic potential of our clinical leads.

Our EDO technology was developed over more than a decade of research into CPPs.

Comparison with Precursor Technologies

In mouse models, we have observed that our delivery peptides retain the robust activity of previous generations of high arginine content CPPs, and yet possess an improved tolerability profile that we believe increases their likelihood of successful clinical translation. During our extensive preclinical assessments of these novel peptides in murine and NHP models, we have succeeded in efficiently delivering nucleic acid payloads to their targets, and have achieved meaningful levels of activity without the dose-limiting toxicities that have traditionally been associated with other peptides in this class of intracellular delivery agents.

In order to demonstrate that our EDO platform possesses an improved therapeutic index over precursor CPPs – in this instance the ‘Pip’ peptides previously developed by Gait and Wood – we assessed the exon skipping efficiency and tolerability of a number of CPP-PMO conjugates in wild-type mice by utilizing the well-established ASO sequence that skips exon 23 of the murine dystrophin mRNA. As seen in the figure below, we observed in this study that the EDO conjugates retained the high levels of activity seen with the Pip conjugates – over 75% exon skipping was observed in the tibialis anterior, or TA, when measured by RT-PCR following a single dose of 30 mg/kg – while the post-administration urinary levels of Kidney Injury Molecule-1, or KIM-1, a marker of renal toxicity, were reduced by a factor of over 100. Thus, we believe that our EDO technology potentially possesses a wider therapeutic index than these precursor CPPs, which we believe supports the further development and clinical translation of our product candidates and platform.

Our EDO technology has a wider therapeutic index than precursor CPP-PMOs. Graph plotted as mean ± SEM, n = 10 per group for saline control; 3 per group for Pip-PMO conjugate; 6 per group for EDO conjugate.

We believe that this finding represents a true step-change in the CPP field. While traditional CPPs traded activity for tolerability, often because they contained a high absolute number and concentration of arginine residues, our novel delivery peptides are designed to decouple this relationship. We believe the unique structural characteristics of the EDO peptides allow this class of CPPs to retain impressive cell penetration and oligonucleotide delivery while mitigating the unacceptable toxicities seen with earlier generations of CPPs, including the Pips. In driving our pipeline forward, we are seeking to leverage these critical characteristics with the goal of developing a safe and effective portfolio of EDO therapeutics.

Comparison with Other Oligonucleotide Delivery Technologies in Development

Other CPP-PMO approaches

There are a number of other peptide-mediated approaches that are currently being developed for the delivery of oligonucleotide therapeutics. Of these, we have, through an extensive review of publicly available presentations and patent applications, hypothesized that the most clinically advanced peptide-based delivery approach for oligonucleotides utilizes the cell-penetrating properties of a hexa-arginine sequence with an additional glycine residue. We refer to this CPP as R6G herein and have conducted extensive head-to-head preclinical studies to compare the biodistribution and activity of our model of this moiety with our novel EDO peptides.

We have observed robust in vivo activity of our EDO technology in a number of animal models, with this activity being significantly higher when compared to our model of the competing R6G approach. In a head-to-head preclinical study conducted in wild-type mice using the established exon 23-skipping antisense oligonucleotide, a single 10 mg/kg intravenous dose of our EDO conjugate resulted in exon skipping levels in the TA that were four-fold higher than those induced by the R6G conjugate at the same dose when measured by RT-PCR seven days after dosing. In a repeat-dose preclinical study in mice, three 30 mg/kg intravenous doses of our EDO conjugate every two weeks resulted in exon skipping levels in the heart that were seven-fold higher than those of the R6G conjugate, also dosed three times at 30 mg/kg, when measured by RT-PCR seven days after the last dose. We believe the higher level

of exon skipping achieved in this study supports the ability of our EDO technology to successfully deliver oligonucleotides to cardiac tissue, which in turn provides us with an opportunity to address the primary cause of death in DMD patients.

In preclinical studies, single and multiple doses of our EDO conjugate led to increased exon skipping compared to the R6G conjugate. Graphs plotted as mean ± SEM; **** denotes extremely significant, p < 0.0001; n = 5 per group for single dose activity, n = 8 per group for repeat dose activity.

Antibody-oligonucleotide approaches

In addition to the CPP-PMO approaches described above, a number of groups are 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, including:

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More efficient tissue penetration due to the small size of our EDO delivery peptides relative to an antibody or antibody fragment;

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The ability to deliver across the blood-brain barrier to the CNS;

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Limited immunogenicity or risk of complement activation due to the considerably lower protein load associated with our EDO peptides; and

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A scalable, facile, fully-synthetic manufacturing process with no cell-based steps that is supported by a readily-characterizable drug product.

We believe these benefits support the further development and clinical translation of our suite of EDO product candidates and underpin our robust competitive position in the neuromuscular and neurologic disease space.

Improved Biodistribution of the EDO platform

We believe that our EDO platform has the potential to achieve robust delivery of cargo therapeutics to a very broad range of target tissues, a characteristic that may provide a critical advantage for our technology in the neuromuscular and neurologic disease space. Following a single intravenous dose of PGN-EDO51 in NHPs, quantifiable levels of PMO were observed in muscle tissues throughout the body one week after administration, including in cardiac muscle, as well as in brain tissues such as cerebral cortex and cerebellum. We believe this broad biodistribution highlights the potential of our technology to deliver to critical yet difficult-to-reach

tissue types like cardiac muscle, and robustly positions our EDO platform in the treatment of diseases with multi-systemic pathologies, like DMD and DM1.

A single administration of PGN-EDO51 in NHPs led to tissue exposure of the cargo PMO therapeutic in muscle and brain tissue one week after dosing. Graph plotted as mean ± SEM; n = 2 per group; CC = cerebral cortex, LLOQ = lower limit of quantification.

Furthermore, we are particularly excited by the potential of this technology to deliver therapeutic agents to the CNS with intravenous dosing. While the levels of the cargo PMO in the cerebral cortex and cerebellum are lower than for the other tissue types investigated, this biodistribution study provides robust evidence to suggest that our peptides are capable of delivering conjugated cargo moieties across the blood-brain barrier, a characteristic which may in turn allow us to address the CNS phenotypes that are evident in DM1 patients. In addition, we believe that this result supports the future development of EDO therapeutics for neurologic indications, and work is ongoing to further understand the ability of our EDO platform technology to deliver cargos to various regions of the brain and CNS.

Scalable Manufacturing Process

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 highly scalable and easily characterizable – attributes that we will seek to leverage to support the rapid development and clinical translation of our EDO conjugate therapeutics. We have produced, manufactured and released multiple cGMP batches, and have successfully utilized this material in a Phase 1 clinical trial.

We have developed a robust manufacturing process for our EDO product candidates.

Accelerated and Efficient Pipeline Development

Our initial preclinical programs leverage the same EDO peptide to enhance the delivery and cellular and nuclear uptake of oligonucleotide therapeutic candidates. We intend to apply our deep understanding of our EDO platform and current preclinical programs to support the rapid development of additional product candidates for other neuromuscular and neurologic indications. We believe that the ability of our EDO peptides to deliver exon skipping therapeutics to muscle cells, including cardiac muscle cells, is largely independent of the exact sequence of the PMO. Therefore, by leveraging our existing preclinical data and the plug-and-play nature of our EDO platform, we believe that we are well-positioned to rapidly develop additional product candidates with the potential to drive clinically relevant therapeutic outcomes across a wide variety of tissue types. We have observed the validity of this approach with one of our product candidates by moving from concept to completion of an NHP study in less than 18 months.

Our Portfolio: An Initial Focus on Neuromuscular Diseases

We anticipate expanding this pipeline to include other neuromuscular targets, along with opportunities in neurologic indications, and we will seek to leverage the modular, scalable nature of our EDO technology to support our rapid 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. PGN-EDO51 is designed to splice out exon 51 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. In a Phase 1 clinical trial of PGN-EDO51, we observed the highest levels of exon skipping and oligonucleotide in humans following a single dose, when compared to publicly available data for other exon 51 skipping approaches. In wild-type NHP studies, at tolerable doses, we have observed what we believe is the highest rate of exon 51 skipping in skeletal muscles, including diaphragm, based on cross-trial comparisons with publicly available data for any approved therapeutic or known developmental candidate. Furthermore, in head-to-head studies conducted in wild-type NHPs, we found that PGN-EDO51 had greater activity than R6G-PMO at the same dose level, a comparator compound which we believe to be structurally equivalent to Sarepta’s SRP-5051, the most clinically advanced peptide-ASO conjugate. In the mdx mouse model, we observed the highest level of

dystrophin production in skeletal muscle following a single dose of PGN-EDO23, the murine analogue of PGN-EDO51, when compared to other clinical-stage DMD therapeutic candidates. Our Phase 1 clinical trial also indicated that PGN-EDO51 was generally well-tolerated at pharmacologically relevant dose levels. In 2023, we anticipate opening two clinical trials in DMD patients amenable to an exon 51 skipping. CONNECT1-EDO51 is an open-label MAD study to open in Canada in the first half of 2023, with initial dystrophin, exon skipping and safety data anticipated in 2024. CONNECT2-EDO51 is a multinational, randomized, placebo-controlled MAD clinical trial anticipated to open in the second half of 2023, and is designed to potentially support a future accelerated approval pathway.

Disease background and prevalence

DMD is a debilitating X-linked recessive 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 live male births, and it is invariably fatal by young adulthood. There are up to 15,000 DMD patients in the United States, approximately 25,000 DMD patients in Europe and approximately 5,000 in Japan.

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.

DMD is a progressive disease 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. 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 therapeutic approach, and thus the estimated exon 51 patient population is approximately 2,000 in the United States, 3,200 in Europe and 700 in Japan.

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

Current approaches and limitations

There is no cure for DMD and there are no treatments that have clinically demonstrated a meaningful impact on disease progression. 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. Ataluren is a small molecule that enables the dystrophin protein synthesis machinery to bypass nonsense mutations, where a stop codon is introduced into the dystrophin messenger RNA, or mRNA, thus preventing the synthesis of full-length dystrophin protein. This drug, marketed by PTC Therapeutics, Inc., or PTC as Translarna, has received conditional approval in a number of countries outside of the United States, including across the European Economic Area. However, an approval has yet to be granted by the U.S. Food and Drug Administration, or FDA.

An alternative approach 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 antisense oligonucleotide, or 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 therapeutic 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 the European Union, or EU or in Japan on the basis of this minimal degree of dystrophin restoration as a surrogate endpoint.

In addition to oligonucleotide therapeutics, gene therapy approaches are also in clinical development as potential treatments for DMD. For example, Sarepta is developing SRP-9001 in collaboration with Roche for the potential treatment of ambulant patientswith DMD and in September 2022 submitted a biologics license application or BLA to the U.S. Food and Drug Administration (FDA) for accelerated marketing approval. 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 ‘microdystrophin’ genes with an unclear functional benefit, where >50% 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:

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

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

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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.

Our approach

We are developing a portfolio of 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 activity observed with PGN-EDO51 in the clinic in healthy volunteers and in preclinical models. We believe the higher levels of exon skipping obtained with PGN-EDO51 in healthy volunteers and in NHPs when compared to published and head-to-head data for other such therapies is directly related to the ability of our EDO platform to drive the tissue penetration, cellular uptake and nuclear delivery of the PMO cargo therapeutic to the subcellular compartment where interaction with the mRNA takes place.

Our preclinical data

Activity data: Substantial improvements in exon skipping levels

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 each of the model systems evaluated. In DMD patient cells bearing a deletion of exon 52, where an exon 51-skipping modality restores the open reading frame and facilitates the production of dystrophin, treatment with PGN-EDO51 resulted in high levels of exon 51 skipping across a wide range of concentrations. These results suggest that our first product candidate has the potential to drive robust exon skipping activity in a highly relevant in vitro environment and thus supported the advancement of this product candidate to further studies in in vivo models.

The mdx mouse, a well-characterized model of DMD, has been widely employed in the field to assess the potential activity of therapeutic candidates for this indication. The pathologies evident in the mdx mouse model arise due to the presence of a point mutation in exon 23 of the murine dystrophin gene, leading to the production of a dystrophin transcript in which the open reading frame is disrupted. As in DMD patients, this disruption precludes production of a functional dystrophin protein, and as a result mdx mice exhibit extensive cell death, fibrosis and muscle tissue degeneration.

We have utilized PGN-EDO23, a murine analogue of PGN-EDO51, to assess the activity of our EDO platform in mdx mice. PGN-EDO23 consists of our lead EDO peptide conjugated to the well-established exon 23-skipping PMO, and thus the activity of this compound is highly applicable to PGN-EDO51, and our pipeline candidates PGN-EDO53, PGN-EDO45 and PGN-EDO44.

Creatine kinase, or CK, is a critical biomarker of muscle damage, with this enzyme being elevated in DMD patients from birth. In the absence of dystrophin, the structural integrity of the sarcolemma, or muscle cell membrane, is disrupted, leading to the release of CK into the blood. Following intravenous administration of a single, generally well-tolerated dose of 30 mg/kg or 60 mg/kg of PGN-EDO23, we observed normalization of serum CK to wild-type levels in mdx mice seven days post-dose. The normalization of CK levels observed in this study suggest that PGN-EDO23 may restore muscle cell integrity and prevent further damage in mdx mice

under a single dose regimen, and we believe that this outcome supports the potential therapeutic utility of PGN-EDO51 in the treatment of DMD patients.

A single dose of PGN-EDO23, the murine analogue of PGN-EDO51, was observed to normalize creatine kinase, a marker of muscle damage in mdx mice. Graph plotted as mean ± SEM; **** = p ≤ 0.0001, ns = p ≥ 0.05; n = 3 for control groups, n = 5 for treated group.

In addition to this significant reduction in CK, we also observed high levels of exon 23 skipping and dystrophin production in mdx mice when measured by RT-PCR and Western blot, respectively, seven days after a single dose of PGN-EDO23. In the quadriceps, a single, generally well-tolerated dose of 60 mg/kg yielded an exon skipping rate of 86.3% and dystrophin restoration to 90.4% of wild-type levels, while in the biceps the same dose resulted in 93.1% exon skipping and 99.7% dystrophin restoration. In the diaphragm, this dosing regimen afforded an exon skipping rate of 76.6% and dystrophin restoration levels of 80.6%, and in the critical cardiac tissues the exon skipping rate was observed to be 62.3%, with dystrophin restoration levels of 25.7%.

We subsequently conducted a repeat-dose study where 30 mg/kg of PGN-EDO23 was intravenously administered to mdx mice once, twice, three or four times every four weeks, with tissue collection and analysis four weeks following the final dose. In the biceps, the level of exon 23 skipping was observed to be 91.5% after four doses when measured by RT-PCR, a value that was 1.7 times higher than that observed following a single dose. Dystrophin production was measured by western blot, and was observed to reach a level of 82.3% in the same tissue after four doses. In comparison, a level of 22.5% was 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 four-weekly dosing regimen for PGN-EDO51, and serves to highlight our belief that dystrophin production is likely to increase with subsequent doses in DMD patients.

Given the relevance of the mdx mouse as a preclinical model for DMD, we believe that these robust exon skipping and dystrophin readouts are supportive of the potential activity of the EDO platform in this disease and the potential clinical benefit we may deliver to patients with our lead candidate, if approved. In addition, the levels of dystrophin production we observed in mdx

skeletal muscles were higher than the levels obtained by other clinical-stage DMD therapeutic candidates, with this cross-trial comparison further highlighting what we believe to be the potentially best-in-class nature of our approach.

Robust exon skipping and dystrophin restoration was observed with repeat dosing of PGN-EDO23 in mdx mice. Graph plotted as mean ± SD; n = 4-5 for each group; grey band represents dystrophin LLOQ (2.5%).

We have 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.

In a preclinical intravenous dose study, we observed that a single administration of PGN-EDO51 in NHPs led to high rates of exon 51 skipping in the TA, diaphragm and heart, with these tissues being harvested seven days post-dose and then assayed using a RT-PCR protocol. Of particular note are the results obtained for the heart, where exon skipping rates of 18.6%, 45.8% and 86.7% were observed following single doses of 20, 40 and 60 mg/kg respectively. In the TA, exon skipping levels of 57.6% were observed following a single dose of 20 mg/kg, while the diaphragm yielded levels of 70.7% at the same dose. We believe the results obtained in this study for PGN-EDO51 represent the highest rate of exon 51 skipping in primate skeletal muscles, including diaphragm, following a single administration at tolerable target dose levels of any approved therapeutic or known development candidate.

Single doses of PGN-EDO51 led to high rates of exon 51 skipping in a preclinical NHP study. Graph plotted as mean ± SEM; n = 2 per group.

In order to benchmark the ability of our lead EDO peptide to improve the tissue penetration, cellular uptake and nuclear delivery of oligonucleotide therapeutics, we carried out a study comparing our EDO-conjugated PMO to an R6G peptide conjugated to the same PMO. We have conducted a considerable number of benchmarking studies of PGN-EDO51 against this conjugate, and we believe – based on publicly-available information – that R6G-PMO is structurally equivalent to SRP-5051, Sarepta’s CPP-PMO product candidate that is currently in clinical development for the treatment of DMD patients who are amenable to an exon 51-skipping approach. In this preclinical study, NHPs were dosed intravenously with either PGN-EDO51, R6G-PMO or a saline control three times with an interval of two weeks between doses. Biopsies of the biceps and quadriceps were collected seven days after the first and second dose, and tissues were harvested seven days after the final dose.

Through RT-PCR analysis of key skeletal muscles collected by biopsy seven days after the first dose, we observed markedly higher exon skipping levels for PGN-EDO51 when compared to R6G-PMO. At 30 mg/kg, a single dose of PGN-EDO51 afforded an exon 51 skipping level of 43.6% in the biceps, which was 7.9 times higher than the level of 5.5% observed for R6G-PMO. In the quadriceps, this differential was 10 times, with 44.9% exon 51 skipping observed for PGN-EDO51, and just 4.5% for R6G-PMO.

Single dose administration of PGN-EDO51 yielded considerably higher exon skipping levels than R6G-PMO. Graph plotted as mean ± SD; n = 3 per group; study was not powered for statistical significance.

Following three bi-weekly doses of 30 mg/kg, we observed robust exon skipping activity for PGN-EDO51, with levels of greater than 70% obtained in key skeletal muscles following analysis by RT-PCR seven days after the final dose. In biceps, an exon 51 skipping level of 77.5% was obtained; and in quadriceps, 73.4%. In patients with DMD, cardiomyopathy and subsequent heart failure is a leading cause of death, and predominantly involves the left ventricle, the chamber responsible for pumping oxygenated blood around the body. In addition to these cardiac pathologies, DMD patients also experience a progressive impairment in pulmonary

function due to the impact of the dystrophic process on the respiratory muscles, including the diaphragm, which in turn results in significant morbidity and mortality over time. We observed 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 our lead candidate to address the key pathologies that are evident in DMD.

In addition to cardiac pathologies, DMD patients also experience a progressive impairment in pulmonary function due to the impact of the dystrophic process on the respiratory muscles, including the diaphragm, which in turn results in significant morbidity and mortality over time. In the critical diaphragm tissue, a 10 mg/kg repeat dose of PGN-EDO51 afforded exon skipping rates in NHPs that were approximately 12-fold higher than those observed for R6G-PMO. No serious adverse events were observed during this study.

Preclinical repeat dose administration of PGN-EDO51 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.

In order to understand the potential accumulation of exon 51-skipped transcripts under a four-weekly, or Q4W, repeat dose regimen, we assessed NHP tissue samples of the biceps collected seven days following a single administration of PGN-EDO51, and compared these with samples of the biceps collected seven days following four administrations of PGN-EDO51 every four weeks. The levels of exon 51 skipping of the DMD transcript were assayed via an RT-PCR protocol and a droplet digital PCR, or ddPCR, protocol. The results obtained showed a robust accumulation in the levels of the exon 51 skipped transcript between one doses and four doses under both PCR protocols. Following four doses of 20 and 30 mg/kg, exon 51 skipping levels were measured by RT-PCR to be 68.6% and 80.6% respectively, with these levels being 1.8 times and 2.1 times higher than for a single dose. Under a ddPCR assay, these levels were 34.9% and 37.6% following four doses at 20 and 30 mg/kg respectively, which were 14 times and 2.6 times

higher than for a single dose. We believe this accumulative effect suggests that the activity of PGN-EDO51 is likely to increase with chronic dosing in DMD patients, which further supports the clinical potential of our lead candidate in this devastating disease.

Exon skipped transcripts in the biceps accumulated under a preclinical repeat-dose regimen of PGN-EDO51 when assessed by RT-PCR and ddPCR. Graph plotted as mean ± SD; n = 3-8 per group; study was not powered for statistical significance.

To provide context to our NHP data, we believe it is important to consider data presented by Sarepta for SRP-5051, which we understand to be structurally equivalent to the R6G-PMO conjugate we used as a comparator in our preclinical studies. In a Phase 2 clinical trial of SRP-5051 in DMD patients amenable to an exon 51-skipping approach, Sarepta reported that patients treated with 30 mg/kg of their candidate achieved dystrophin production of 6.55% of normal levels. A dose response was observed in this trial, with patients dosed at 30 mg/kg achieving twice as much dystrophin production as patients treated with 20 mg/kg. A positive relationship was observed between exon skipping levels and dystrophin expression, with higher exon skipping resulting in higher dystrophin expression.

In our head-to-head study in NHPs, PGN-EDO51 dosed at 10 mg/kg resulted in near equivalent exon skipping to the 30 mg/kg dose of R6G-PMO, and PGN-EDO51 dosed at 30 mg/kg resulted in significantly higher exon skipping than R6G-PMO at the same dose. Given these results, we believe that PGN-EDO51 at the 10 mg/kg dose has the potential to afford comparable dystrophin levels to those obtained following treatment with SRP-5051 at the 30 mg/kg dose in DMD patients. We believe that doses of PGN-EDO51 above 10 mg/kg could generate even greater dystrophin than obtained for the 30 mg/kg dose of SRP-5051, which may lead to clinically meaningful outcomes for those suffering from this disease. Due to the long half-life of the dystrophin protein, and the accumulation in exon skipping that we observed during our repeat-dose study, we believe that these levels could continue to accumulate over time and thus further enhance the clinical benefit afforded to DMD patients by our EDO technology.

PGN-EDO51 was observed to generate greater dystrophin than SRP-5051 in NHPs supporting its potential in DMD patients.*

*Clinical data included in drug label (FDA). **Source: Sarepta MOMENTUM study update, 20 and 30 mg/kg cohort, 03May21.

*** Comparative statements are based on cross-trial comparisons with publicly-available data for other exon skipping approaches that have been assessed following a single dose. **** Source: Sarepta 2022 10-K filing.

In addition to Sarepta’s competing SRP-5051 approach, several organizations focused on the development of next-generation oligonucleotide therapeutics have released NHP exon skipping data. Dyne, a clinical-stage company utilizing an antigen-binding fragment, or Fab, as a delivery vector for nucleic acid species, announced NHP data in the fourth quarter of 2021 for DYNE-251, their lead product candidate for the treatment of DMD patients amenable to an exon 51-skipping approach. Following two bi-weekly or four weekly doses of 30 mg/kg, with tissue analysis two weeks or one week, respectively, after the final dose, Dyne reported very minimal levels of exon skipping in quadriceps, diaphragm and whole heart. An administration regimen of five weekly doses of 30 mg/kg, with tissue analysis four weeks after the final dose, yielded more robust results: 18% exon 51 skipping in quadriceps, 52% in diaphragm and 43% in whole heart. While this data was not obtained as part of a head-to-head comparison, we reported exon 51-skipping levels of 73.4% in the quadriceps and 75.9% in the diaphragm following a dosing regimen of three bi-weekly doses of 30 mg/kg of PGN-EDO51 with tissue analysis one week after the final dose, and 18.6% in whole heart and 70.7% in diaphragm following a single dose of 20 mg/kg of PGN-EDO51 with tissue analysis one week after dosing. These NHP results serve to further cement our belief that PGN-EDO51 has the potential to address multiple, critical muscle types in this competitive space.

We are additionally aware of other cell-penetrating peptide and antibody-conjugated approaches in development for the treatment of DMD patients amenable to exon 44- and exon 45-skipping therapeutic approaches.

Preclinical tolerability data: Generally well-tolerated through clinically relevant dose levels

PGN-EDO51 was generally well-tolerated in single-dose, 28-day Good Laboratory Practice, or GLP, toxicity studies in mice and NHPs; no treatment-related mortality and no serious adverse events were observed through the therapeutic dose range. There were no adverse microscopic observations and no adverse impacts on clinical chemistry markers at clinically relevant dose levels.

An in vitro T cell stimulation assay conducted with peripheral blood mononuclear cells from healthy donors indicated that PGN-EDO51 has a very low immunotoxicity risk. This is further supported by data showing that the pharmacokinetic profile of PGN-EDO51 was similar following the first and third dose, suggesting no significant neutralizing anti-drug antibody responses were present after a three-dose regimen in NHPs.

We submitted our preclinical dataset for PGN-EDO51, including both pharmacology and toxicity studies, to Health Canada as part of our CTA filing in the first quarter of 2022. Upon review, Health Canada subsequently authorized our CTA.

Clinical development

Phase 1 healthy volunteer study: highest levels of exon skipping and oligonucleotide delivery in humans following a single dose

In the third quarter of 2022, we completed a first-in-human, Phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose 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 droplet digital PCR, or ddPCR, assay.

Target engagement (exon skipping in biceps): A dose dependent increase in exon skipping was observed in biceps, with the levels obtained being the highest observed in humans following a single dose, based on cross-trial comparisons with publicly available data for other exon 51 skipping approaches.

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In the 10 mg/kg dose cohort, PGN-EDO51 exhibited mean exon skipping of 1.1% and 1.4% in biceps biopsies taken at Day 10 (n=6) and Day 28 (n=6), respectively;

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In the 15 mg/kg dose cohort, PGN-EDO51 exhibited mean exon skipping of 1.4% and 2.0% in biceps biopsies taken at Day 10 (n=5) and Day 28 (n=6), respectively.

We observed the highest levels of exon skipping in humans following a single dose based on cross-trial comparisons with publicly available data for other exon 51 skipping approaches. Data is shown as mean ± SD; n = 6 for PGN-EDO51 (n = 5 for D10 at 15 mg/kg), n = 8 for placebo. Asterisks indicate values that were under the lower level of quantification.

Pharmacokinetics (tissue concentration in biceps); A dose-dependent increase in PGN-EDO51 tissue concentration was observed in biceps, with the levels obtained being the highest observed in humans for a DMD therapeutic following a single dose, based on cross-trial comparisons with publicly available data for other exon 51 skipping approaches.

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In the 10 mg/kg dose cohort, PGN-EDO51 exhibited mean oligonucleotide tissue concentrations of 19 nM and 11 nM in biceps biopsies taken at Day 10 (n=6) and Day 28 (n=6), respectively;

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In the 15 mg/kg dose cohort, PGN-EDO51 exhibited mean oligonucleotide tissue concentrations of 50 nM and 50 nM in biceps biopsies taken at Day 10 (n=5) and Day 28 (n=6), respectively.

High, persistent tissue concentrations of oligonucleotide were observed. Data is shown as mean ± SD; n = 6 for PGN-EDO51 (n = 5 for D10 at 15 mg/kg), n = 8 for placebo. Asterixis indicate values that were under the lower level of quantification.

We believe that the exon skipping and tissue concentration 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. Furthermore, Sarepta’s recent clinical trials of SRP-5051 provide a relevant benchmark with regards to exon skipping target engagement in healthy adults. We note here that, in a single dose trial in HV, administration of SRP-5051 resulted in median exon skipping levels of <0.2%. However, in a subsequent multiple ascending dose trial in DMD patients, treatment with SRP-5051 yielded exon skipping levels that were multiple times higher at the same dose level. Thus, based on this precedent, we anticipate that the exon skipping rates afforded by PGN-EDO51 when administered to patients have the potential to exceed the rates when administered to HVs.

Safety and tolerability: The trial met its primary endpoint, providing evidence that PGN-EDO51 was generally well tolerated at clinically relevant doses. 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, 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;

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There was no evidence of hypomagnesemia.

There were transient, reversible changes in kidney biomarkers that resolved without intervention at higher doses. 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. Transient mild (Grade 1) to moderate (Grade 2) hypomagnesemia was observed in two participants at the 15 mg/kg dose and did not require any intervention. Under this Phase 1 protocol 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 oligo levels and exon skipping levels in muscle observed at 5 mg/kg and 10 mg/kg, further dose escalation was not deemed necessary by the sponsor.

TEAEs were mild and resolved without intervention at clinically relevant doses. Asterix denotes that no Grade 4 or 5 TEAEs were recorded.

In prior multiple ascending dose NHP studies, we observed that kidney biomarker elevations were reduced with subsequent administrations, a finding that supports the potential tolerability of PGN-EDO51 with repeat dosing. In one such study, three doses of PGN-EDO51 were administered intravenously to NHP over 30 minutes every second week, and serum chemistry markers were assessed 2 days and 14 days after each dose. Following the first administration, an elevation in key kidney biomarkers was observed at Day 2; this elevation was completely resolved by Day 14. Following the second and third administrations, the Day 2 elevations seen previously were ameliorated, and we believe it to be likely that this attenuation in acute kidney biomarker elevations may also be observed in human clinical trial participants under a repeat-dose regimen.

In NHP, an amelioration of elevations in kidney biomarkers was observed with repeat dosing of PGN-EDO51. Graph plotted as mean ± SD; n = 3 per group; grey bar shows normal range.

Sarepta noted that hypomagnesemia, a condition in which there is a low level of magnesium in the body, was observed in DMD patients at a dose levels of 10, 20 and 30 mg/kg of SRP-5051 in their repeat-dose clinical trials, an observation that is consistent with our own findings in repeat-dose preclinical testing of R6G-PMO. We have also observed hypomagnesemia as a side effect of PGN-EDO51 at doses above the therapeutic range, both in healthy volunteers following a single dose of 15 mg/kg, and in NHPs following multiple administrations.

Sarepta has initiated what it reports could be the pivotal trial for SRP-5051, with a protocol that includes magnesium supplementation. Sarepta has further noted that this modulation in clinical chemistry may be reversible, monitorable and manageable with prophylactic oral administration of such supplements. Based on these findings, we anticipate that we may also observe hypomagnesemia following repeat-dose administration of PGN-EDO51 in our patient clinical trials. We intend to carefully monitor serum magnesium levels in our upcoming Phase 2 patient clinical trials.

Phase 2 MAD studies in exon 51 skipping-amenable DMD patients

The readouts obtained from our Phase 1 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 trial of PGN-EDO51 in patients. Based on these inputs, we have designed what we believe to be an efficient and informative clinical path to evaluate 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-EDO51, to be conducted in Canada and a larger, global, randomized, double-blind placebo-controlled MAD study, CONNECT2-EDO51. We anticipate opening CONNECT1-EDO51 in the first half of 2023, with initial dystrophin, exon skipping and safety data in 2024. CONNECT2-EDO51 is expected to open in the second half of 2023, and will potentially be a registrational trial, subject to alignment with regulatory authorities.

Our Phase 2 clinical development plan for PGN-EDO51 is designed to support a potential accelerated approval pathway.

We believe that this clinical path may enable us to pursue an accelerated approval pathway for PGN-EDO51 with the FDA. A product candidate may 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 and is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. In the DMD space, the FDA has approved four drugs under the accelerated approval pathway since 2016. If we receive positive results from our Phase 2 trials for PGN-EDO51 that show an acceptable tolerability profile; a clinically meaningful increase in dystrophin levels, a surrogate endpoint in the biceps of DMD patients; and robust exon skipping levels in the same tissue, we intend to pursue discussions with the FDA for an accelerated approval pathway.

Four drugs have received accelerated approval in DMD to date.

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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 cytosine-uracil-guanine, or CUG, trinucleotide repeat expansion present in the DMPK mRNA, thus reducing the ability of these trinucleotide repeats to sequester MBNL1, a critical RNA processing protein. This approach – which is not designed to knock down DPMK – 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 ex vivo, we observed that treatment with PGN-EDODM1 led to the robust correction of multiple downstream mis-spliced transcripts and a reduction in toxic nuclear foci. In our in vivo preclinical studies, a single dose of PGN-EDODM1 was observed to correct the molecular and functional phenotypes presented in the human skeletal actin – long repeat, or HSALR, mouse model of disease, ameliorating downstream mis-splicing events, reversing myotonia and normalizing mobility. We also observed that the molecular correction effected by PGN-EDODM1 in this preclinical mouse model exhibited a durability of effect that was in excess of six months. Furthermore, the tissue concentrations of oligonucleotide that were found to be pharmacologically active in the HSALR mouse model were similar to those observed for PGN-EDO51 in human muscle in a Phase 1 clinical trial, supporting the ability of PGN-EDODM1 to achieve potentially therapeutic levels of oligonucleotide in the clinic. We anticipate opening a single ascending dose clinical trial of PGN-EDODM1, FREEDOM-DM1 in DM1 patients in the first half of 2023, with functional assessments, correction of mis-splicing and safety data expected in 2024.

Disease background and prevalence

DM1 is a monogenic, autosomal dominant, progressive disorder that primarily affects skeletal, cardiac and smooth muscles, with 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 United States, 75,000 patients in Europe and 15,000 patients in Japan. However, under- and mis-diagnosis 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; cardiac pathologies; 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 myotonic dystrophy protein kinase, or DMPK, gene. Specifically, DM1 is caused by an expansion in the number of cytosine-thymine-guanine, or 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:

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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 DPMK 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 have muscle weakness and cardiac arrhythmia, with an average lifespan of 48 years 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. There are a number of therapeutics currently in clinical development for the treatment of DM1 symptoms, including the small molecules tideglusib and ERX-963. However, neither of these therapeutics treat the underlying cause of disease, and thus we believe that a considerable unmet need will remain in DM1 even if these therapies are approved. 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 tissue 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 monoclonal antibodies, or mAbs, and antigen-binding fragments, or Fabs, that target the transferrin receptor 1, or TfR1, in order to deliver cargo oligonucleotides. In contrast to our mechanism of action, where MBNL1-DMPK transcript binding is disrupted, these AOCs are designed to knockdown DMPK as a therapeutic modality. However, such knockdown or degradation approaches that cannot differentiate between expanded and non-expanded transcripts may risk confounding effects due to 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. This condition can be created artificially by the degradation of RNA levels to such an extent that there is no longer sufficient protein produced 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.

We believe that PGN-EDODM1 has the potential to offer a number of benefits when compared to these alternative technologies, as outlined in the table below:

Our approach is differentiated against competing AOC DPMK knockdown therapeutics in development for DM1.

EDO CONJUGATE TFR1 FAB / MAB AOC

We are additionally aware of other cell-penetrating peptide approaches currently in preclinical development for the treatment of DM1.

Our approach

Our product candidate for the treatment of DM1, PGN-EDODM1, consists of our lead EDO cell penetrating peptide conjugated to an ASO that binds to the CUG repeats 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, i.e. the sequestration of MBNL1 due to the high number of CUG repeats 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 DPMK transcript 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 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 target DMPK for knockdown.

Preclinical data

Activity data: Correction of molecular and functional DM1 phenotype

There is a considerable variation in the CTG repeat length present in DM1 patients, with patient population genotypes ranging from 50 repeats to almost 3,000. In order to demonstrate the potential ability of PGN-EDODM1 to address pathologies across this population, we have conducted our preclinical studies in models with a wide range of CTG repeat lengths that encompass those observed in the patient population. We have observed robust activity for PGN-EDODM1 across this spectrum from studies conducted in DM1 patient cells with 2,600 CTG repeats, to studies in the HSALR mouse model, with 220 – 250 CTG repeats. We believe that this finding supports the clinical potential of PGN-EDODM1 in DM1 and highlights the relevance of this therapeutic approach to patients carrying long and short CTG repeat expansions.

PGN-EDODM1 activity has been observed in preclinical models with a wide range of CTG repeat lengths.

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 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 ribonuclear 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 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 a preclinical study conducted in DM1 patient cells, PGN-EDODM1 treatment supported the reduction of pathogenic nuclear foci in a dose-dependent fashion. Graph plotted as mean ± SD; n = 3-4 per group.

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 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 DPMK transcript, resulting in a reduction in the number of nuclear foci and the liberation of MBNL1.

PGN-EDODM1 treatment resulted in the liberation of MBNL1 from DPMKfoci.

Treatment of DM1 patient cells with PGN-EDODM1 supported the robust correction of multiple downstream mis-spliced transcripts associated with key disease pathologies in a dose-dependent fashion. Utilizing RT-PCR and capillary electrophoresis analysis, an accurate, high resolution quantification methodology, we assessed the transcription profiles of MBNL1 and MBNL2, where pathogenic inclusion of exon 5 can result in further splicing defects; BIN1, where inclusion of exon 7 in DM1 patients can lead to altered excitation-contraction coupling and thus muscle weakness; LDB3, where exclusion of exon 11 may lead to dilated cardiomyopathy in DM1 patients; and SORBS1, where inclusion of exon 24 can result in altered insulin handling in the disease state. At the highest dose assessed, 20 μM, PGN-EDODM1 was observed to effect robust mis-splicing correction, resulting in exon inclusion or exclusion rates of approximately 70% of healthy control levels in these transcripts. This observation supports our therapeutic hypothesis that treatment with PGN-EDODM1 may restore the altered global spliceopathy profiles seen in DM1 patients to that of a healthy individual, thus ameliorating the key pathologies that are the hallmark of this devastating disease. In contrast, treatment with the unconjugated PMO at a dose level of 20 μM afforded very limited correction of downstream mis-splicing events,

and we believe this result further supports the criticality of our EDO platform in delivering therapeutic cargos to their nuclear site of action.

In an in vitro study, PGN-EDODM1 treatment resulted in correction of mis-splicing pathologies to around 70% of healthy control levels. Graph plotted as mean ± SD; n = 5 per group.

Building on the success of these in vitro studies, we utilized the HSALR mouse model of DM1 to assess the activity of PGN-EDODM1. This well-validated transgenic mouse model contains between 220 and 250 CTG trinucleotide repeats in the inserted human skeletal actin 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 errant inclusions or exclusions of exons.

Sequestration of MBNL1 in the HSALR mouse model causes mis-splicing of multiple RNAs including Clcn1 and Atp2a1, both of which are involved in the regulation of muscle movement. This mis-splicing causes the mice to exhibit myotonia, effectively recapitulating the classic symptom of disease that is observed in DM1 patients. Mis-splicing of Atp2a1 manifests as a lack of exon 22 inclusion in the Atp2a1 mRNA when compared to wild-type splicing patterns, while mis-splicing of Clcn1 manifests as an increase in exon 7a inclusion in the Clcn1 mRNA when compared to wild-type splicing patterns. Following a single intravenous administration of PGN-EDODM1, we observed dose-dependent normalization of the splicing of these genes in the quadriceps and gastrocnemius

muscles two weeks after dosing. At a dose of 30 mg/kg, we achieved 91% correction of Atp2a1 mis-splicing and 68% correction of Clcn1 mis-splicing, highlighting the potential of our product candidate to address such downstream pathologies.

PGN-EDODM1 led to a dose-dependent normalization of the splicing of Atp2a1 and Clcn1 transcripts in preclinical study in quadriceps muscles in HSALR mice. Graph plotted as mean ± SEM; n = 8 for PGN-EDODM1 group, n = 16 for HSALR saline control, n = 8 for WT saline control; **** = p≤0.0001.

Consistent with the reversal of mis-splicing events, treatment with a single dose of PGN-EDODM1 also led to a complete reversal of the myotonia phenotype in HSALR mice, with a dose of 30 mg/kg showing complete normalization two weeks after administration. In observational studies we noted quantitative amelioration of myotonia, where treated mice were able to ambulate normally following the inducement of this functional phenotype of disease by hindlimb pinching. In contrast, untreated HSALR mice were unable to efficiently use their hind legs and dragged them behind following the same myotonic inducement event.

PGN-EDODM1 led to a complete amelioration of myotonia in a preclinical study after a single administration. Graph plotted as min to max; n = 8 for PGN-EDODM1 group, n = 16 for HSALR saline control, n = 8 for WT saline control; *** = p≤0.001.

The pharmacologic effects of PGN-EDODM1 were observed to be highly durable. In a duration of effect study, again in the HSALR mouse model, amelioration of the pathogenic splicing patterns of the Atp2a1 and Clcn1 transcripts in the gastrocnemius and quadriceps persisted for at least 24 weeks following a single 30 mg/kg intravenous administration of PGN-EDODM1.

PGN-EDODM1 led to durable improvements in mRNA splicing through 24 weeks post-dose in the HSALR mouse model. Graph plotted as mean ±SEM; n = 7 for 0 timepoint, 8 for 2- and 12-week timepoints; 5 for 24-week timepoint.

The clinical potential of PGN-EDODM1 is further supported by the readouts from our recently completed Phase 1 clinical trial of PGN-EDO51. In this trial, we observed tissue concentrations following a single dose of 10 mg/kg that were comparable to those observed in the HSALR mouse model following a single, pharmacologically active dose of 30 mg/kg. Based on this correlation, we believe that PGN-EDODM1 has the potential to achieve oligonucleotide tissue concentrations in DM1 patients that could lead to clinically meaningful outcomes, a factor which supports the further development of this product candidate.

PGN-EDO51 tissue concentrations were comparable to those achieved for PGN-EDODM1 in HSALR mice. Graph plotted as mean ± SEM; n = 8 for PGN-EDODM1 group, n = 8 for WT saline control; n = 6 for PGN-EDO51 data.

Preclinical tolerability data: Well-tolerated through 90 mg/kg in NHP

We have completed a number of rigorous studies that support a well-tolerated safety profile for PGN-EDODM1. In an in vitro study, immortalized myoblasts from a DM1 patient with 2,600 CTG repeats were differentiated for 4 days to myotubes and treated for 24 hours with PGN-EDODM1 at a range of concentrations between 1 and 20 μM. DMPK transcript levels were evaluated by qPCR and normalized to Rplp0. In NHPs, three doses of 10, 30 or 60 mg/kg of PGN-EDODM1 were administered every two weeks. One week following the final dose, DMPK transcript levels were evaluated by qPCR and normalized to Rplp0.

In both DM1 patient cells and in NHPs, mean DMPK transcript levels remained unchanged relative to an untreated control, and we believe that these results indicate that PGN-EDODM1, as designed, does not target DMPK transcripts for degradation. This unique mechanism of action is a potentially important safety benefit, as such an approach does not carry the risk of possible confounding effects due to the knockdown of DMPK.

No significant changes in mean DMPK transcript levels were observed in DM1 patient cells or in NHPs. Graphs plotted as mean ± SEM; n = 4 for patient cell data, n = 3-4 for NHP data.

We have also assessed the potential for off-target effects in our preclinical work, and have not found any evidence of such findings in any of the studies conducted. In a single-dose study conducted in the HSALR mouse model, where PGN-EDODM1 was administered intravenously at a dose level of 30 mg/kg, we observed no short- or long-term impacts on the levels of other, non-DMPK transcripts containing more than 10 CUG repeats. Transcript levels were measured by qPCR, and were subsequently normalized to Rplp0. This study extended to a 24-week timepoint, and we believe that the data obtained suggests that there is limited risk of off-target complications for this approach in DM1 patients.

No significant impact was observed on the mean levels of other transcripts containing more than 10 CUG repeats. Graphs plotted as mean ± SEM; n=7 for 0 timepoint, 8 for 2- and 12-week timepoints; 5 for 24-week timepoint; NT = not treated, T = treated.

Finally, in single-dose GLP toxicology studies conducted in NHP, PGN-EDODM1 was observed to be well-tolerated through dose levels of 90 mg/kg. There were no adverse effects on kidney, liver or cardiovascular function, and we believe that the totality of the data obtained from these preclinical and IND-enabling studies highlight a potentially favorable safety profile for PGN-EDODM1 and support the further progression of this product candidate to the clinic. We anticipate opening a single ascending dose clinical trial of PGN-EDODM1 in DM1 patients in the first half of 2023, with functional assessments, correction of mis-splicing and safety data expected in 2024.

Clinical development

Our clinical development program for PGN-EDODM1 has been designed to identify a clinically active dose while providing what we believe to be the shortest path to a potential approval. Our planned Phase 1 SAD study in DM1 patients, FREEDOM-DM1, is expected to be a randomized, double-blind placebo-controlled study that will provide critical information regarding the safety of escalating doses of PGN-EDODM1. Other anticipated readouts for this study include functional assessments and correction of mis-splicing data, which we expect to deliver in 2024. The data from our Phase 1 SAD trial is intended to support our planned Phase 2 randomized, double blind, placebo-controlled MAD study in DM1, which we anticipate opening in 2024. This study will incorporate functional assessments, correction of mis-splicing and safety readouts, and will be designed to support potential accelerated regulatory approvals.

We anticipate opening our first clinical trial in DM1 patients in the first half of 2023, with clinical readouts in 2024.

Additional DMD programs

Overview

We are developing additional EDO therapeutics for further DMD patient populations, including PGN-EDO53, for the 8% of DMD patients who are amenable to an exon 53-skipping approach, PGN-EDO45, for the 8% of DMD patients who are amenable to an exon 45-skipping approach, and PGN-EDO44, for the 6% of DMD patients who are amenable to an exon 44-skipping approach. These programs utilize the same EDO cell penetrating peptide as our exon 51-skipping product candidate, PGN-EDO51, which we believe will allow us to leverage our drug development experience in this indication to rapidly drive our exon 53, 45 and 44-skipping product candidates to the clinic. In a NHP study of PGN-EDO53, we observed single-dose exon skipping levels that were almost seven times higher than those observed for R6G-PMO53, a relevant comparator peptide-PMO conjugate approach. For PGN-EDO45, high, dose-dependent levels of exon skipping were observed in wild-type human myoblasts, with our nominated candidate outperforming the R6G-PMO45 comparator at every dose level assessed. Finally, our PGN-EDO44 nominated candidate also exhibited high, dose-dependent levels of exon skipping in wild-type human myoblasts.

Disease background and prevalence

DMD is a fatal X-linked recessive disorder that occurs in up to 1 in 3,500 live male births, with estimates suggesting that there are up to 15,000 DMD patients in the United States and approximately 25,000 in Europe and 5,000 in Japan. Afflicted individuals

carry a mutation in the dystrophin gene, and the resulting absence of this critical protein in muscle tissue leads to cell death, atrophy and progressive motoric weakness. As such, DMD sufferers experience a continual deterioration in their physical abilities from birth onwards, with most boys requiring the use of a wheelchair by their early teens. Cardiomyopathies and respiratory ailments become increasingly common as the disease takes hold, and most patients will die from these complications between the ages of 25 and 35. It is estimated that 8% of DMD patients have mutations that would be amenable to treatment with an exon 53-skipping approach, with exon 45- and 44-skipping approaches targeting a further 8% and 6% of the DMD patient population respectively.

Current approaches and limitations

Two unconjugated ASOs leveraging PMO chemistry have been approved for the treatment of individuals with DMD who are amenable to an exon 53-skipping approach – golodirsen, marketed as VYONDYS 53® by Sarepta and viltolarsen, marketed as VILTEPSO® by NS Pharma in the U.S. and Nippon Shinyaku in Japan. These drugs were approved in the United States through the accelerated approval regulatory pathway based on an increased expression of dystrophin, which is considered to be a surrogate endpoint for this indication. Both golodirsen and viltolarsen have yet to establish a clinical benefit for DMD patients through a confirmatory trial. For the exon 45 patient population, casimersen, marketed as AMONDYS 45® by Sarepta, has also been approved in the United States through the accelerated approval pathway, with a confirmatory trial yet to be completed for this unconjugated PMO. There are no approved therapeutics for the exon 44 patient population.

Our approach

We are developing PGN-EDO53, a peptide-conjugated ASO designed to skip exon 53 of the dystrophin transcript in DMD patients who are amenable to such a therapeutic approach. We have employed the same EDO peptide in PGN-EDO53 as is utilized in PGN-EDO51, our exon 51-skipping product candidate – a factor that allows us to rapidly drive our exon 53-skipping product candidate forward by leveraging our drug development experience with this peptide and in this indication. Similarly, PGN-EDO45 and PGN-EDO44, our peptide-conjugated ASOs designed to skip exons 45 and 44 of the DMD transcript respectively, also leverage the capabilities of our lead EDO peptide.

Preclinical development

PGN-EDO53

We have completed a preclinical in vitro screen of a number of candidate ASO sequences utilizing the established PMO chemistry. We synthesized a number of exon 53-skipping PMOs conjugated to our lead EDO peptide and assessed the activity of these in human-derived myoblasts carrying mutations that are amenable to treatment with an exon 53-skipping therapeutic approach. Based on the data obtained from this in vitro screen, we have subsequently assessed several development candidates in a repeat-dose NHP study, where these PPMOs were assessed alongside a relevant comparator, R6G-PMO53. Three doses of each PPMO were administered intravenously over 60 minutes every four weeks, with biopsies of the biceps collected 5 to 7 days after the first and second administrations, and terminal samples collected 7 days after the final dose. Exon 53 skipping was assessed by RT-PCR.

Notably, the single-dose exon skipping levels of 36.4% obtained for the selected PGN-EDO53 candidate were almost seven times higher than those observed for the R6G-PMO53 comparator at 5.4%. Furthermore, exon 53 skipped transcripts accumulated with repeat dosing of PGN-EDO53 – following the third and final dose of PGN-EDO53, mean exon skipping levels were observed to be 57.2%, a level that was nearly three-times higher than the mean exon skipping levels of 20.8% that were observed for the R6G-PMO53 comparator. We believe that this accumulation in skipped transcript is indicative of the potential of the EDO platform to drive clinically meaningful levels of exon skipping, and ultimately dystrophin production, in DMD patients.

Treatment with PGN-EDO53 afforded single-dose exon skipping levels almost seven times higher than for a comparator PPMO. Graphs plotted as mean ± SD; n = 3 per group; study was not powered for statistical significance.

PGN-EDO45 and PGN-EDO44

We have completed an in vitro screen for our PGN-EDO45 and PGN-EDO44 programs in order to nominate potential candidates for further development. In these studies, wild-type human myoblasts were treated for 48 hours with the PPMO compounds, and exon 45 or exon 44 skipping levels were assessed by RT-PCR. For PGN-EDO45, we observed high, dose-dependent levels of exon 45 skipping, with this product candidate outperforming a R6G-PMO45 comparator compound at each dose level assessed. At the highest dose, PGN-EDO45 demonstrated mean exon 45 skipping levels of 79.9%, while R6G-PMO45 demonstrated only 54.0%. For PGN-EDO44, high, dose-dependent levels of exon 44 skipping were also observed, with a readout of 93.4% obtained at the highest dose. No comparator compound was included in this study.

High levels of exon skipping were observed for PGN-EDO45 and PGN-EDO44 in wild-type human myoblasts. Graphs plotted as mean ± SD; n = 4 for PGN-EDO45 and R6G-PMO (n = 3 for R6G-PMO at two top dose levels), n = 3 for PGN-EDO44.

We believe that these data highlight the ability of our EDO technology to enable the rapid development of our pipeline programs, and support the modularity of this approach.

Expanding the Application and Scope of Our EDO Platform

New indications with PMO therapeutics

We intend to apply our deep understanding of our EDO platform and PMO therapeutics to the development of additional product candidates in other indications. We believe that the ability of our EDO peptides to deliver exon skipping therapeutics to muscle cells, including cardiac muscle cells, as well as to the CNS, is largely independent of the exact sequence of the PMO. As such, by leveraging the preclinical data we have previously obtained and the “plug-and-play” nature of our EDO platform, we believe that we are well-positioned to develop additional product candidates that have the potential to drive clinically relevant therapeutic outcomes in other neuromuscular indications as well as in neurologic indications. We have observed the potential of this approach with our PGN-EDO53 program, where we progressed from concept through to NHP study initiation in less than a year.

New cargos

We believe that our EDO technology has the potential to facilitate the delivery of multiple oligonucleotide therapeutics. To date, our efforts have primarily focused on the delivery of PMOs, but we are now actively pursuing 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. We will leverage our deep expertise in this field to design new peptides that target specific tissue types, and will seek to further optimize the tissue and cellular delivery of our EDO platform.

Manufacturing

We do not own or operate manufacturing facilities, and currently rely on third-party contract manufacturing organizations, or CMOs, and suppliers for the cell-penetrating peptide, linker and oligonucleotide components that compromise 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 CMOs 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 CMOs are able to assemble either the peptide intermediate, the linker, and/or the oligonucleotide as well as the final API.

There are extensive regulations that govern the manufacturing of biopharmaceutical products, and the third-party manufacturing organizations we work with are required to adhere to these. Our CMOs are required to manufacture our product candidates under current Good Manufacturing Practice, or 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. Individuals with DMD also use prednisone or prednisolone off-label. In addition, there are four FDA-approved exon skipping drugs: EXONDYS 51 (Eteplirsen), VYONDYS 53 (Golodirsen) and AMONDYS 45 (Casimersen), which are naked PMOs approved for the treatment of DMD patients amenable to exon 51, exon 53 and exon 45 skipping, respectively, and are 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. Companies focused on developing treatments for DMD that target dystrophin, as our DMD program does, include PTC with ataluren, a small molecule targeting nonsense mutations in a Phase 3 clinical trial, Sarepta with SRP-5051, a peptide-linked PMO currently being evaluated in a Phase 2b clinical trial for patients amenable to exon 51 skipping, Daiichi Sankyo Company, Limited with DS-5141b, an exon skipping approach for Exon 45 currently in clinical development, Dyne, with DYNE-251, an antibody-conjugated PMO that targets exon 51 skipping in a Phase 1/2 clinical trial, BioMarin Pharmaceutical Inc. with BMN-351, a phosphorothioate oligonucleotide that targets exon 51 skipping currently in preclinical development, Wave Life Sciences Ltd. with WVE-N531, a stereopure oligonucleotide in clinical development for patients amenable to exon 53 skipping, Nippon Shinyaku with NS-089/NCNP-02, an oligonucleotide that targets exon 44 skipping that is currently in clinical development, Avidity Biosciences, Inc., or Avidity, which is in Phase 1/2 clinical development with AOC 1044, an antibody oligonucleotide conjugate that targets Exon 44 skipping, and Entrada Therapeutics, Inc., which is in preclinical development with ENTR-601-44, a peptide-oligonucleotide conjugate that targets Exon 44 skipping and with a clinical hold placed on its investigational new drug application (IND) by the FDA prior to dosing of the first healthy volunteer.

In addition, several companies are developing gene therapies to treat DMD, including Pfizer Inc. (PF-06939926), currently being evaluated in a Phase 3 clinical trial, Sarepta (SRP-9001 and Galgt2 gene therapy program), with the former currently being evaluated in a Phase 3 clinical trial and with a BLA under review by the FDA for accelerated approval, Solid Biosciences Inc. (SGT-003), currently in preclinical development, and REGENXBIO Inc (RGX-202), currently in clinical development. Gene editing treatments that are in preclinical development are also being pursued by Vertex Pharmaceuticals Incorporated, or Vertex, Sarepta and Eli Lilly and Company. We are also aware of several companies targeting non-dystrophin mechanisms for the treatment of DMD, including Edgewise Therapeutics, Inc., with EDG-5506, a muscle stabilizer that is currently in clinical development.

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PEPG · 10-K · period ended 2022-12-31

Item 1. Business.

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PEPG · 10-K · period ended 2022-12-31

Item 1. Business.

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