PepGen Announces Positive Data from Low-Dose Cohort of PGN-EDO51 in Ongoing CONNECT1-EDO51 Phase 2 Clinical Trial for Treatment of Duchenne Muscular Dystrophy
PepGen Inc. (Nasdaq: PEPG) announced positive clinical data from the first dose cohort (5 mg/kg) of PGN-EDO51, its lead candidate for Duchenne muscular dystrophy (DMD) patients amenable to exon 51-skipping. In the CONNECT1-EDO51 Phase 2 trial, PGN-EDO51 showed:
- Mean exon skipping levels of 2.15% after three months
- Mean muscle-adjusted dystrophin level of 1.49%, a 0.70% increase from baseline
- Mean absolute dystrophin level of 0.61%, a 0.26% increase from baseline
The 5 mg/kg dose was well-tolerated, with all patients continuing to the long-term extension. Dosing of the second cohort at 10 mg/kg is ongoing. PepGen plans to optimize the design of the CONNECT2 Phase 2 trial based on these results.
PepGen Inc. (Nasdaq: PEPG) ha annunciato dati clinici positivi dal primo gruppo di dosaggio (5 mg/kg) del PGN-EDO51, il suo principale candidato per i pazienti affetti da distrofia muscolare di Duchenne (DMD) suscettibili al skipping dell'esone 51. Nello studio clinico CONNECT1-EDO51 di Fase 2, il PGN-EDO51 ha mostrato:
- Livelli medi di skipping degli esoni del 2,15% dopo tre mesi
- Livello medio di distrofina corretta per la massa muscolare dell'1,49%, un aumento dello 0,70% rispetto al valore iniziale
- Livello assoluto medio di distrofina dello 0,61%, un aumento dello 0,26% rispetto al valore iniziale
La dose di 5 mg/kg è stata ben tollerata, con tutti i pazienti che hanno continuato con l'estensione a lungo termine. La somministrazione del secondo gruppo a 10 mg/kg è attualmente in corso. PepGen prevede di ottimizzare il design dello studio CONNECT2 di Fase 2 basandosi su questi risultati.
PepGen Inc. (Nasdaq: PEPG) anunció datos clínicos positivos del primer grupo de dosis (5 mg/kg) del PGN-EDO51, su principal candidato para pacientes con distrofia muscular de Duchenne (DMD) susceptibles a la omisión del exón 51. En el ensayo clínico de Fase 2 CONNECT1-EDO51, PGN-EDO51 mostró:
- Niveles promedio de omisión de exones del 2.15% después de tres meses
- Nivel medio de distrofina ajustado al músculo del 1.49%, un aumento del 0.70% respecto a la línea de base
- Nivel absoluto medio de distrofina del 0.61%, un aumento del 0.26% respecto a la línea de base
La dosis de 5 mg/kg fue bien tolerada, con todos los pacientes continuando hacia la extensión a largo plazo. La dosificación del segundo grupo a 10 mg/kg está en curso. PepGen planea optimizar el diseño del ensayo CONNECT2 de Fase 2 basado en estos resultados.
PepGen Inc. (Nasdaq: PEPG)는 51번 엑손 건너뛰기 대상인 샘플을 위한 주요 후보 PGN-EDO51의 첫 번째 용량 코호트(5 mg/kg)로부터 긍정적인 임상 데이터를 발표했습니다. CONNECT1-EDO51 2상 시험에서 PGN-EDO51은 다음과 같은 결과를 보였습니다:
- 3개월 후 평균 엑손 건너뛰기 수준 2.15%
- 근육 조정된 평균 득톡신 수준 1.49%, 기준선 대비 0.70% 증가
- 절대 평균 득톡신 수준 0.61%, 기준선 대비 0.26% 증가
5 mg/kg 용량은 잘 견뎌졌으며, 모든 환자가 장기 연장에 계속 참여했습니다. 10 mg/kg에서 두 번째 코호트 투약이 진행 중입니다. PepGen은 이러한 결과에 기반하여 CONNECT2 2상 시험의 설계를 최적화할 계획입니다.
PepGen Inc. (Nasdaq: PEPG) a annoncé des données cliniques positives du premier groupe de dose (5 mg/kg) de PGN-EDO51, son principal candidat pour les patients atteints de dystrophie musculaire de Duchenne (DMD) pouvant bénéficier du saut d'exon 51. Dans l'essai CONNECT1-EDO51 de Phase 2, PGN-EDO51 a montré:
- Niveaux moyens de saut d'exons de 2,15% après trois mois
- Niveau moyen de dystrophine ajusté en fonction de la masse musculaire de 1,49%, une augmentation de 0,70% par rapport à la ligne de base
- Niveau moyen absolu de dystrophine de 0,61%, une augmentation de 0,26% par rapport à la ligne de base
La dose de 5 mg/kg a été bien tolérée, tous les patients poursuivant l'extension à long terme. L'administration du deuxième groupe à 10 mg/kg est en cours. PepGen prévoit d'optimiser la conception de l'essai CONNECT2 de Phase 2 en fonction de ces résultats.
PepGen Inc. (Nasdaq: PEPG) hat positive klinische Daten aus der ersten Dosierungskohorte (5 mg/kg) des PGN-EDO51, seinem Hauptkandidaten für Patienten mit Duchenne-Muskeldystrophie (DMD), die für das Exon-51-Skipping geeignet sind, bekannt gegeben. Im CONNECT1-EDO51 Phase 2-Studie zeigte PGN-EDO51:
- Durchschnittliche Exon-Skipping-Niveaus von 2,15% nach drei Monaten
- Durchschnittlicher muskeladjustierter Dystrophinspiegel von 1,49%, eine Steigerung von 0,70% gegenüber dem Ausgangswert
- Durchschnittlicher absoluter Dystrophinspiegel von 0,61%, ein Anstieg von 0,26% im Vergleich zum Ausgangswert
Die Dosis von 5 mg/kg wurde gut vertragen, und alle Patienten setzten die Langzeitverlängerung fort. Die Dosierung der zweiten Kohorte mit 10 mg/kg läuft derzeit. PepGen plant, das Design der CONNECT2 Phase 2-Studie basierend auf diesen Ergebnissen zu optimieren.
- PGN-EDO51 achieved mean exon skipping levels of 2.15% after three months at 5 mg/kg dose
- Mean muscle-adjusted dystrophin level increased by 0.70% from baseline
- Mean absolute dystrophin level increased by 0.26% from baseline
- The 5 mg/kg dose was well-tolerated with no discontinuations or dose reductions
- All patients from the 5 mg/kg cohort continued to the long-term extension phase
- Dosing of the second cohort at 10 mg/kg is ongoing
- None.
Insights
The recent data from PepGen's CONNECT1-EDO51 Phase 2 trial for PGN-EDO51 in Duchenne muscular dystrophy (DMD) patients is promising. The 5 mg/kg dose showed a mean exon skipping level of
The dystrophin production data is also encouraging. The mean muscle-adjusted dystrophin level reached
However, it's important to note that while these increases are statistically significant, the clinical relevance of these dystrophin levels remains to be determined. Typically, dystrophin levels above
The safety profile appears favorable, with no major adverse events reported. This bodes well for the ongoing evaluation of the higher 10 mg/kg dose. The continuation of all patients into the long-term extension portion of the trial is also a positive sign.
Overall, these early results are encouraging, but larger studies with longer follow-up periods will be necessary to fully assess the efficacy and safety of PGN-EDO51 in DMD patients.
PepGen's announcement of positive data from the CONNECT1-EDO51 Phase 2 trial is likely to be viewed favorably by investors. The company's lead candidate, PGN-EDO51, has demonstrated promising efficacy and safety results at the 5 mg/kg dose level, which could potentially position it as a competitive therapy in the Duchenne muscular dystrophy (DMD) market.
Key financial implications to consider:
- Market Potential: The global DMD market is projected to reach
$4.11 billion by 2023. If PGN-EDO51 continues to show superior results, it could capture a significant market share. - Competitive Advantage: The higher exon skipping levels achieved by PGN-EDO51 compared to other oligonucleotide therapies at similar doses could provide a competitive edge, potentially leading to higher pricing power and market penetration.
- Development Pipeline: Positive results from this trial may increase confidence in PepGen's Enhanced Delivery Oligonucleotide platform, potentially boosting the value of their entire pipeline.
- Future Funding: These encouraging results could make it easier for PepGen to secure additional funding or partnerships for further development and commercialization efforts.
However, investors should remain cautious as these are early-stage results from a small cohort. The outcome of the 10 mg/kg cohort and the larger CONNECT2 trial will be important in determining the long-term value proposition of PGN-EDO51. Additionally, the company's cash runway and burn rate should be closely monitored as they progress through clinical development.
– PGN-EDO51 at 5 mg/kg was well tolerated, and all patients continued to long-term extension portion of trial. Dosing of second cohort at 10 mg/kg is ongoing –
– Four doses of PGN-EDO51 at 5 mg/kg achieved mean exon skipping levels of
– PGN-EDO51 at 5 mg/kg showed mean muscle-adjusted dystrophin level of
– PGN-EDO51 at 5 mg/kg showed mean absolute dystrophin level of
– Conference call scheduled for 4:30 p.m. ET –
“We are encouraged by the early data from our CONNECT1 clinical trial of PGN-EDO51 in people with DMD. In three months, the starting monthly dose of 5 mg/kg achieved high levels of exon skipping and all patients showed increases in dystrophin. PGN-EDO51 produced meaningfully higher levels of exon skipped transcript at lower doses and in a shorter time period compared to other exon 51 therapies, approved and in development, indicating that our Enhanced Delivery Oligonucleotide technology is delivering higher levels of oligonucleotide to the nuclei,” said James McArthur, Ph.D., President and CEO of PepGen. “Importantly, PGN-EDO51 has demonstrated a favorable safety profile, supporting our ongoing evaluation of the 10 mg/kg monthly dose cohort in CONNECT1. We intend to leverage the early observations from CONNECT1 to optimize our CONNECT2-EDO51 Phase 2 trial. Based on these initial results, we are optimistic about the possibility that higher levels of dystrophin production will be observed in the 10 mg/kg cohort of CONNECT1. We also look forward to reporting data from the first cohort of our placebo-controlled multinational study CONNECT2.”
“People with DMD and their families constantly hope for effective therapies with the potential to change the course of this relentlessly progressive neuromuscular disease. I was pleased to see that the 5 mg/kg dose was well tolerated and that all three participants demonstrated an increase in dystrophin production and exon skipping after only three months of treatment with PGN-EDO51. I look forward to seeing the results of exon skipping and dystrophin production at 10 mg/kg in both CONNECT1 and CONNECT2,” said Dr. Hugh McMillan, Pediatric Neurologist at the Children’s Hospital of
CONNECT1 Results for the 5 mg/kg Starting Dose Cohort (n=3)
Exon 51 Skipping and Dystrophin Production Data
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Exon 51 Skipping: PGN-EDO51 produced mean exon skipping in biceps tissue of
2.15% at week 13 compared to baseline. Compared to a receptor mediated delivery technology which delivered comparable levels, on a per-dose basis, of oligonucleotide to muscle tissue, we believe the levels of exon skipping generated by PGN-EDO51 at 5 mg/kg suggest PGN-EDO51 has the potential to be considerably more potent.1
-
Dystrophin Production
-
PGN-EDO51 achieved a mean muscle-adjusted dystrophin level of
1.49% of normal and a0.70% change from baseline after 4 doses, measured at week 13. -
PGN-EDO51 achieved a mean absolute dystrophin level of
0.61% of normal and a0.26% change from baseline after 4 doses, measured at week 13 by Western blot analysis.
-
PGN-EDO51 achieved a mean muscle-adjusted dystrophin level of
Safety and Tolerability Data
The 5 mg/kg dose of PGN-EDO51 was well tolerated by all study cohort participants through week 13. There were no discontinuations, dose interruptions or dose reductions.
- The one related treatment-emergent adverse event was mild and resolved.
- There was no sustained elevation in kidney biomarkers. There were no cases of hypomagnesemia or hypokalemia. There were also no changes in electrolytes or hepatic function and no cases of anemia or thrombocytopenia.
- All three patients in this cohort are continuing to be dosed with PGN-EDO51 at 5 mg/kg in the long-term extension (LTE) phase of the clinical trial. PGN-EDO51 continues to be well tolerated during the LTE as of July 29, 2024.
The Company plans to present additional results from the 5 mg/kg cohort at a medical meeting later in the year.
Update on PGN-EDO51 10 mg/kg Cohort
As of July 29, 2024, two participants have received a total of four doses at 10 mg/kg in the ongoing CONNECT1 study. To date, PGN-EDO51 has been generally well tolerated at this dose level and the Company expects to report initial results from the 10 mg/kg cohort in early 2025.
Update on CONNECT2-EDO51 Clinical Trial
Based on the data from CONNECT1, including PGN-EDO51’s emerging safety profile to date, the Company is working to optimize the design of the CONNECT2 Phase 2 double-blind, placebo-controlled 25-week multinational trial. The CONNECT2 clinical trial is open in the
Conference Call Details
PepGen will host a conference call and webcast today at 4:30 p.m. ET to review the data being presented. To access the call, please dial (866) 400-0049 and provide the Conference ID 9666330. A live webcast of the presentation will be available on the Events & Presentations section of the PepGen investor website, investors.pepgen.com.
About PGN-EDO51
PGN-EDO51, PepGen's lead clinical candidate for the treatment of Duchenne muscular dystrophy (DMD), utilizes the Company's proprietary Enhanced Delivery Oligonucleotide (EDO) technology to deliver a therapeutic phosphorodiamidate morpholino oligomer (PMO) that is designed to target the root cause of this devastating disease. PGN-EDO51 is designed to skip exon 51 of the dystrophin transcript, an established therapeutic target for approximately
About the CONNECT Clinical Program
CONNECT1-EDO51 is an open-label, multiple ascending dose Phase 2 trial designed to evaluate PGN-EDO51 at up to three different dose levels starting with 5 mg/kg administered intravenously once every four weeks for 12 weeks in patients with DMD amenable to an exon 51-skipping approach. The key endpoints for this trial are safety, dystrophin production and exon skipping. Multiple pharmacokinetic parameters are also being assessed as part of the trial protocol.
CONNECT2-EDO51 is a double-blind, placebo-controlled, multiple ascending dose, multinational Phase 2 trial designed to evaluate PGN-EDO51 at up to three different dose levels intravenously once every four weeks for 24 weeks in patients with DMD amenable to an exon 51-skipping approach. Endpoints included in this trial are safety, dystrophin production, exon skipping and clinical assessments of mobility, pulmonary function and quality of life.
About Duchenne Muscular Dystrophy (DMD)
DMD is an X-linked recessive muscle-wasting disease that predominantly affects males. This progressively debilitating and fatal disease is caused by genetic mutations in the gene encoding dystrophin, a protein critical for healthy muscle function, and is one of the most prevalent rare genetic diseases, with an incidence rate of approximately one in every 3,500 to 5,000 male births. DMD is characterized by progressive muscle weakness, which leads to patients losing the ability to walk, a loss of upper body function, cardiac issues and difficulties breathing. DMD is invariably fatal by young adulthood. Despite significant advances in treatments for this devastating disease, current exon skipping therapies are limited by poor delivery to muscle tissue nuclei and have yet to establish meaningful clinical benefit for DMD patients.
About PepGen
PepGen Inc. is a clinical-stage biotechnology company advancing the next-generation of oligonucleotide therapies with the goal of transforming the treatment of severe neuromuscular and neurological diseases. PepGen’s 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 conjugated oligonucleotide therapeutics. Using these EDO peptides, we are generating a pipeline of oligonucleotide therapeutic candidates designed to target the root cause of serious diseases.
For more information, please visit www.pepgen.com. Follow PepGen on LinkedIn and X.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, statements regarding the therapeutic potential and safety profile of PGN-EDO51 based on early data, the potential of our EDO platform to deliver higher levels of oligonucleotide to the nuclei, our expectations regarding the potential for increased levels of exon skipping and dystrophin production following dosing at 10 mg/kg with a longer treatment period, the design, initiation and conduct of clinical trials, including expected timelines for our CONNECT2 Phase 2 trial, the expected timing for additional data reports from our CONNECT1 trial, and ongoing and planned regulatory interactions.
Any forward-looking statements in this press release are based on current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to risks related to: delays or failure to successfully initiate or complete our ongoing and planned development activities for our product candidates, including PGN-EDO51; our ability to enroll patients in our clinical trials, including CONNECT1-EDO51 and CONNECT2-EDO51; that our interpretation of clinical and preclinical study results may be incorrect, or that we may not observe the levels of therapeutic activity in clinical testing that we anticipate based on prior clinical or preclinical results; our product candidates, including PGN-EDO51, may not be safe and effective or otherwise demonstrate safety and efficacy in our clinical trials; adverse outcomes from our regulatory interactions, including delays in regulatory review, clearance to proceed or approval by regulatory authorities with respect to our programs, including clearance to commence planned clinical studies of our product candidates, or other regulatory feedback requiring modifications to our development programs, including in each case with respect to our CONNECT1-EDO51 and CONNECT2-EDO51 programs; changes in regulatory framework that are out of our control; unexpected increases in the expenses associated with our development activities or other events that adversely impact our financial resources and cash runway; and our dependence on third parties for some or all aspects of our product manufacturing, research and preclinical and clinical testing. Additional risks concerning PepGen’s programs and operations are described in our most recent annual report on Form 10-K and quarterly report on Form 10-Q that are filed with the SEC. PepGen explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
- DYNE-251 DELIVER clinical data update, May 20, 2024
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Investors
Dave Borah, CFA
SVP, Investor Relations and Corporate Communications
dborah@pepgen.com
Media
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Lyra Strategic Advisory
Jdeutsch@lyraadvisory.com
Source: PepGen Inc.
FAQ
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