Delivering on the Promise of New Modalities: An Interview with James McArthur, President & CEO of PepGen

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As part of WuXi AppTec’s ongoing efforts to collaboratively foster new thinking and actionable approaches in advancing breakthroughs for patients, we have launched a new interview series in 2022 – “Delivering on the Promise of New Modalities” – so leading voices of R&D can share how their approaches are addressing the barriers standing in the way of breakthroughs.

For the next installment of our interview series, James McArthur, Ph.D. joins us as the President and CEO of PepGen Inc. (PepGen), 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. Last year, PepGen raised $112.5 million to develop therapies for neuromuscular and neurologic diseases, including a focus on Duchenne muscular dystrophy (DMD). Earlier this year, PepGen dosed their first participant in a Phase I clinical trial of PGN-EDO51 for the treatment of DMD and in May became a Nasdaq listed public company.

Thank you for joining us today, James! Congratulations on your clinical trial of PGN-EDO51. For the development of therapies for neuromuscular and neurologic diseases, what are the industry-wide challenges in current therapeutic interventions that your company wants to solve?

James: Research and development of therapeutics for rare neuromuscular diseases has advanced significantly, but transformative therapies for diseases like Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) are still lacking. Oligonucleotide drugs have shown considerable potential as a therapeutic class, but challenges associated with their delivery have limited their effectiveness in certain indications. On their own, oligonucleotides are not readily distributed to heart and skeletal muscle, the key affected tissues in neuromuscular diseases, and are not efficiently taken up into these cells. At PepGen, we are developing our EDO platform to address these critical challenges by optimizing the tissue penetration, cellular uptake and nuclear delivery of oligonucleotides. We anticipate that this approach will enhance the therapeutic activity of these therapies, thus delivering on the promise that oligonucleotides have shown in rare neuromuscular indications.

Could you further introduce the EDO platform for our readers? How is it different from existing approaches?

James: Our Enhanced Delivery Oligonucleotide (EDO) platform is founded on over a decade of research and development, and leverages cell-penetrating peptides to improve the uptake and activity of oligonucleotide therapies. Our EDO peptides are engineered to effectively deliver their oligonucleotide cargos to the hard-to-treat tissues affected in neuromuscular and neurologic disorders, such as the heart, skeletal muscle and the central nervous system (CNS), thereby addressing some of the primary challenges that have impeded treatment of these diseases. Our preclinical data, including in non-human primates, suggests that our EDO therapies achieve greater levels of exon skipping and dystrophin production (in DMD) and correction of mis-splicing and myotonia (in DM1) compared to other therapeutic approaches. As such, we believe that our candidates have the potential to enable new, best-in-class treatments for people living with a broad range of severe neuromuscular and neurologic diseases.

What remain to be the critical challenges in realizing the full potential of your new modality? And what are your next key milestones anticipated?

James: The efficacy of oligonucleotide therapeutics in neuromuscular disorders requires balancing the effectiveness of delivery to muscle with the safety and tolerability profile of the therapy. PepGen’s preclinical data indicates the potential of our EDO technology to balance these requirements. We recently initiated a Phase 1 clinical trial in healthy volunteers for our lead DMD candidate, PGN-EDO51, and expect to report initial safety, pharmacokinetic (oligonucleotide delivery to muscle) and target engagement (exon 51 skipping in muscle) data by the end of 2022. We also plan to submit an Investigational New Drug (IND) application for our DM1 candidate, PGN-EDODM1, in the first half of 2023 and initiate trials shortly thereafter. In parallel, we are conducting additional studies to assess the safety and exon skipping activity for our other DMD candidates in development. Our hope is that we can overcome the challenges faced by current therapeutics in this space to bring truly transformative treatments to patients.

If we were to gather here again in 10 or 15 years’ time, what do you think we’re going to be talking about in terms of what we have already achieved in the industry, and what do you think are going to be some of the solutions going forward?

James: Our hope is that in the next 10 to 15 years we will have seen several important advancements in the treatment of complex, rare diseases that require a tailored treatment approach. Our team at PepGen, and many of our colleagues in the industry, are working daily to improve the delivery of biologic drugs, including oligonucleotide therapeutics, to tissues that are currently not accessible or poorly accessible by existing therapies and modalities. The work that we and others in the field are doing to improve delivery and thus address these key challenges will hopefully enable additional innovations, and we anticipate that this will ultimately lead to a broader range of available therapies for patients who remain underserved by current treatment options. Our hope is that the translation of tailored, personalized medicines will become commonplace, and will eventually facilitate a paradigm shift in the way we study and treat rare diseases.

Do you foresee any big breakthroughs in life science industry in the next decade?

James: As mentioned above, we expect the next decade will bring an increase in both the number and range of precision therapy modalities. As new advancements lower the cost of genetic sequencing, clinical trials have expanded to include more diverse populations and healthcare regulation has begun to adopt better coverage for personalized treatments, leading to a shift in patient care. The hope is that these advancements lead to earlier diagnoses for patients, a factor which will in turn accelerate their treatment journey. At PepGen, we are advancing our EDO therapies to treat a range of patients with neuromuscular diseases, a population often fraught with difficult diagnostic journeys and a lack of effective treatment options. The combination of a more rapid path to diagnosis and more tailored treatments will hopefully lead to meaningful breakthroughs in treatment, and in turn allow more patients to access these transformative treatment modalities.

Thank you James for sharing PepGen’s approaches and your insights!

James: My pleasure.


James McArthur, Ph.D.

President and CEO, PepGen

James McArthur currently serves as President and Chief Executive Officer of PepGen and serves on the company’s Board of Directors. James has more than 25 years of industry experience, has cofounded 5 biotechnology companies, 3 of which were acquired, and has served as a Director of two companies through successful initial public offerings. He was founding CEO of Imara, a public company developing therapies for sickle cell disease and beta-thalassemia, co-founder and President of R&D of Cydan, a rare disease accelerator, and founding CSO of Synovex/Adheron, a rheumatology therapy company acquired by Roche. Prior to serving at these companies, James held senior research leadership roles in several pioneering gene and stem cell therapy companies. He was a venture partner at RA Capital and an entrepreneur in residence at HealthCare Ventures. James was previously a post-doctoral fellow at MIT and UC Berkeley working with Drs. David Raulet and Nobel Laureate James Allison, before which he received his PhD in molecular oncology and BSc in biochemistry from McGill University in Montreal.

Forward-Looking Statements of PepGen Inc.

This interview transcript contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, relating to PepGen Inc. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this interview that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, statements regarding the expected timing of the presentation of data from the ongoing Phase 1 study of PGN-EDO51, the filing of an IND application for PGN-EDODM1 and the nomination of development candidates; and statements about our clinical and pre-clinical programs, product candidates, achievement of milestones, and corporate and clinical/pre-clinical strategies.

Any forward-looking statements in this interview are based on current expectations, estimates and projections only as of the date of this interview and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, that we may fail to successfully complete our Phase 1 trial for EDO51 and pre-clinical studies of other product candidates and obtain required approval before commercialization; our product candidates may not be effective; there may be delays in regulatory approval or changes in regulatory framework that are out of our control; our estimation of addressable markets of our product candidates may be inaccurate; we may fail to timely raise additional required funding; more efficient competitors or more effective competing treatment may emerge; we may be involved in disputes surrounding the use of our intellectual property crucial to our success; we may not be able to attract and retain key employees and qualified personnel; earlier study results may not be predictive of later stage study outcomes; and we are dependent on third-parties for some or all aspects of our product manufacturing, research and preclinical and clinical testing. Additional risks concerning PepGen’s programs and operations are described in its registration statement on Form S-1, which is on file with the SEC, and in its most recent quarterly report on Form 10-Q to be filed with the SEC. PepGen explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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