PepGen Announces CONNECT Program Updates
PepGen (Nasdaq: PEPG) provided updates on its CONNECT clinical program for PGN-EDO51 in Duchenne muscular dystrophy (DMD). The CONNECT1-EDO51 Phase 2 trial has fully enrolled its 10 mg/kg cohort (n=4) and continues dosing the 5 mg/kg cohort (n=3). Clinical data from the 10 mg/kg cohort is expected by year-end 2025.
Two participants in the 10 mg/kg cohort experienced asymptomatic hypomagnesemia, now resolved with supplementation. One participant's dosing was paused due to reduced eGFR, though subsequent testing showed normal glomerular filtration rate. Health Canada has allowed continued dosing at current levels but requests additional safety information before further dose escalation.
The CONNECT2-EDO51 Phase 2 trial, open in the UK, received a clinical hold notice from the FDA regarding its US initiation. The company is working with regulators to address safety concerns and dosing questions.
PepGen (Nasdaq: PEPG) ha fornito aggiornamenti sul suo programma clinico CONNECT per PGN-EDO51 nella distrofia muscolare di Duchenne (DMD). La sperimentazione clinica CONNECT1-EDO51 di fase 2 ha completato l'arruolamento del suo gruppo da 10 mg/kg (n=4) e continua a somministrare la dose da 5 mg/kg (n=3). I dati clinici del gruppo da 10 mg/kg sono attesi entro la fine del 2025.
Due partecipanti del gruppo da 10 mg/kg hanno sperimentato ipomagnesemia asintomatica, ora risolta grazie alla supplementazione. La somministrazione di un partecipante è stata sospesa a causa di un eGFR ridotto, sebbene i test successivi abbiano mostrato un tasso di filtrazione glomerulare normale. Salute Canada ha autorizzato la continuazione della somministrazione ai livelli attuali, ma richiede ulteriori informazioni sulla sicurezza prima di un'eventuale incremento della dose.
La sperimentazione clinica CONNECT2-EDO51 di fase 2, attualmente aperta nel Regno Unito, ha ricevuto un avviso di stop clinico dalla FDA riguardo la sua iniziativa negli Stati Uniti. L'azienda sta collaborando con i regolatori per affrontare le preoccupazioni sulla sicurezza e le domande relative alla somministrazione.
PepGen (Nasdaq: PEPG) proporcionó actualizaciones sobre su programa clínico CONNECT para PGN-EDO51 en distrofia muscular de Duchenne (DMD). El ensayo clínico CONNECT1-EDO51 de fase 2 ha completado la inclusión de su cohorte de 10 mg/kg (n=4) y continúa con la dosificación de la cohorte de 5 mg/kg (n=3). Se esperan datos clínicos de la cohorte de 10 mg/kg para finales de 2025.
Dos participantes en la cohorte de 10 mg/kg experimentaron hipomagnesemia asintomática, que ahora se ha resuelto con suplementación. La dosificación de un participante fue pausada debido a una disminución en la eGFR, aunque pruebas posteriores mostraron una tasa de filtración glomerular normal. Health Canada ha permitido la continuación de la dosificación en los niveles actuales, pero solicita información adicional sobre la seguridad antes de un aumento en la dosis.
El ensayo clínico CONNECT2-EDO51 de fase 2, que está abierto en el Reino Unido, recibió un aviso de suspensión clínica por parte de la FDA con respecto a su inicio en EE. UU. La empresa está trabajando con los reguladores para abordar las preocupaciones de seguridad y las preguntas sobre la dosificación.
PepGen (Nasdaq: PEPG)는 듀센느 근육 디스트로피(DMD)를 위한 PGN-EDO51의 CONNECT 임상 프로그램에 대한 업데이트를 제공했습니다. CONNECT1-EDO51 2상 시험은 10 mg/kg 코호트(n=4)의 등록을 완료하였고, 5 mg/kg 코호트(n=3)에 대한 투여를 계속하고 있습니다. 10 mg/kg 코호트에 대한 임상 데이터는 2025년 연말까지 나올 것으로 예상됩니다.
10 mg/kg 코호트의 두 참가자는 무증상 저마그네슘혈증을 경험했으며, 현재는 보충제로 해결되었습니다. 한 참가자의 투여는 eGFR 감소로 인해 일시 중단되었으나, 후속 검사에서 정상적인 사구체 여과율이 나타났습니다. 캐나다 보건부는 현재 수준에서의 지속적인 투여를 허용했으나, 추가 용량 증가 전에 추가적인 안전성 정보를 요청했습니다.
영국에서 개방된 CONNECT2-EDO51 2상 시험은 미국에서의 시작에 대해 FDA로부터 임상 보류 통지를 받았습니다. 회사는 안전성 우려와 투여 질문을 해결하기 위해 규제 기관과 협력하고 있습니다.
PepGen (Nasdaq: PEPG) a fourni des mises à jour sur son programme clinique CONNECT pour PGN-EDO51 dans la dystrophie musculaire de Duchenne (DMD). L'essai clinique CONNECT1-EDO51 de phase 2 a pleinement recruté sa cohorte de 10 mg/kg (n=4) et continue à administrer la cohorte de 5 mg/kg (n=3). Les données cliniques de la cohorte de 10 mg/kg sont attendues d'ici la fin 2025.
Deux participants de la cohorte de 10 mg/kg ont présenté une hypomagnésémie asymptomatique, désormais résolue par supplémentation. L'administration d'un participant a été suspendue en raison d'une réduction de l'eGFR, bien que des tests ultérieurs aient montré un taux de filtration glomérulaire normal. Santé Canada a autorisé la poursuite de l'administration aux niveaux actuels, mais demande des informations supplémentaires sur la sécurité avant une éventuelle escalade de la dose.
L'essai clinique CONNECT2-EDO51 de phase 2, ouvert au Royaume-Uni, a reçu un avis de suspension clinique de la FDA concernant son initiation aux États-Unis. L'entreprise travaille avec les régulateurs pour aborder les préoccupations de sécurité et les questions de dosage.
PepGen (Nasdaq: PEPG) hat Updates zu seinem CONNECT-Klinikprogramm für PGN-EDO51 bei Duchenne-Muskeldystrophie (DMD) bereitgestellt. Die CONNECT1-EDO51 Phase-2-Studie hat ihre Kohorte von 10 mg/kg (n=4) vollständig rekrutiert und setzt die Dosierung der Kohorte von 5 mg/kg (n=3) fort. Klinische Daten aus der Kohorte von 10 mg/kg werden bis Ende 2025 erwartet.
Zwei Teilnehmer in der Kohorte von 10 mg/kg hatten asymptomatische Hypomagnesiämie, die nun durch Supplementierung behoben wurde. Die Dosierung eines Teilnehmers wurde aufgrund eines gesenkten eGFR pausiert, wobei nachfolgende Tests eine normale glomeruläre Filtrationsrate zeigten. Health Canada hat die Fortsetzung der Dosierung auf dem derzeitigen Niveau erlaubt, fordert jedoch zusätzliche Sicherheitsinformationen, bevor eine weitere Dosissteigerung erfolgt.
Die CONNECT2-EDO51 Phase-2-Studie, die im Vereinigten Königreich geöffnet ist, erhielt einen klinischen Haltbescheid von der FDA bezüglich ihres Starts in den USA. Das Unternehmen arbeitet mit den Aufsichtsbehörden zusammen, um Sicherheitsbedenken und Fragen zur Dosierung zu klären.
- All treatment-related adverse events in CONNECT1 have been mild
- Magnesium levels returned to baseline in affected participants
- Nuclear scan showed normal glomerular filtration rate in participant with reduced eGFR
- FDA clinical hold on CONNECT2 trial in the US
- Health Canada halted dose escalation pending safety review
- Dosing paused for one participant due to reduced eGFR
- Additional safety data required before expanding trial enrollment
Insights
This clinical program update reveals both progress and challenges that warrant careful investor consideration. The CONNECT1 trial's enrollment completion in both cohorts (10 mg/kg n=4, 5 mg/kg n=3) represents a milestone, but several developments merit scrutiny:
The safety profile shows complexity: While all adverse events have been classified as mild, the emergence of hypomagnesemia and eGFR concerns, though manageable, has attracted regulatory attention. Health Canada's hesitation regarding dose escalation and new enrollment, coupled with the FDA's clinical hold on CONNECT2, suggests increased regulatory scrutiny that could impact the development timeline.
The program faces a critical juncture with multiple regulatory bodies (FDA, Health Canada, MHRA) taking different stances. This multi-jurisdictional complexity could affect:
- Development timeline extensions
- Additional costs for addressing regulatory requirements
- Potential delays in reaching key milestones
- Competition vulnerability in the DMD space
The maintained timeline for 10 mg/kg cohort data by year-end 2025 provides some stability, but investors should monitor:
- Resolution speed of regulatory concerns
- Impact on patient recruitment and retention
- Potential protocol modifications affecting data comparability
- Cash runway implications of extended development timelines
While the safety signals appear manageable, their emergence at relatively modest doses (10 mg/kg) raises questions about the therapeutic window and potential dose limitations. This could affect competitive positioning against other exon-skipping therapies in development.
CONNECT1-EDO51: Phase 2, open-label, multiple ascending dose (MAD) clinical trial being conducted in
CONNECT1 has enrolled two cohorts of boys and young men living with DMD amenable to exon 51 skipping and its endpoints include safety and tolerability, dystrophin production, exon skipping, and muscle tissue concentration. The 10 mg/kg cohort is fully enrolled (n=4) and participants in the 5 mg/kg cohort (n=3) are continuing to dose at that level in the long-term extension portion of the study. The Company remains on track to report clinical data from the 10 mg/kg cohort by year-end 2025.
Magnesium levels in two of the participants in the 10 mg/kg cohort, who were previously reported as having asymptomatic hypomagnesemia, have returned to baseline levels with administration of ongoing oral magnesium supplementation. Dosing of one of these two participants was paused due to a reduction of his estimated glomerular filtration rate (eGFR). This event did not meet the pre-specified criteria for a dose limiting toxicity. A subsequent nuclear scan indicated measured glomerular filtration rate was in the normal range. The participant’s eGFR is improving and the investigator is evaluating for the resumption of dosing as this value normalizes. The Company is continuing to review the event and associated potential confounding factors to better understand its manifestation.
The Company has received communication from Health Canada that dosing of patients in the 5 and 10 mg/kg cohorts may continue at their current dose levels and has requested additional information from the Company to address Health Canada’s safety concerns before any further dose escalation or enrollment of any additional participants at the current dose levels. The Company is working with Health Canada to address its questions.
CONNECT2-EDO51: Phase 2, multinational, double-blind, placebo-controlled, MAD clinical trial currently open in the
CONNECT2 will enroll boys and young men amenable to exon 51 skipping and its endpoints include safety and tolerability, dystrophin production, exon skipping, and functional outcome measures. In December, the Company announced that it had received a clinical hold notice from the US Food and Drug Administration (FDA) regarding its Investigational New Drug application to initiate the CONNECT2 clinical trial in the US, which was previously authorized to proceed by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The Company is working with the FDA to address its questions regarding supportive data for the dosing levels planned for the patient population.
Paul Streck, MD, Head of R&D, commented, “As of January 23, 2025, all treatment related adverse events in CONNECT1 have been mild, and we believe that the emerging safety profile of PGN-EDO51 remains favorable. We are encouraged that the decreased eGFR reported for one of our CONNECT1 10 mg/kg cohort patients has improved during his brief pause in dosing. We are evaluating the etiology, and we will continue to closely monitor safety in our PGN-EDO51 clinical program. We look forward to providing clinical data updates from both CONNECT1 and our FREEDOM-DM1 study in myotonic dystrophy type 1 during 2025, including initial data from FREEDOM during the first quarter, as well as an update on the status of CONNECT2, as we continue to advance our platform with a focus on addressing patients in need.”
About PGN-EDO51
PGN-EDO51, PepGen's investigational candidate in development for the treatment of DMD, utilizes the Company's proprietary Enhanced Delivery Oligonucleotide (EDO) technology to deliver a therapeutic oligonucleotide 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 PGN-EDODM1
PGN-EDODM1, PepGen's investigational candidate in development for the treatment of myotonic dystrophy type 1 (DM1), utilizes the Company's proprietary EDO technology to deliver a therapeutic oligonucleotide that is designed to restore the normal splicing function of MBNL1, a key RNA splicing protein. DM1 is a progressively disabling, life-shortening genetic disorder. DM1 is estimated to affect 40,000 people in
About PepGen
PepGen 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 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 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 ongoing status of our CONNECT1 and CONNECT2 Phase 2 trials of PGN-EDO51, including recent safety and dosing updates, the expected timing for additional data reports from our CONNECT1 Phase 2 trial, and our data from our FREEDOM Phase 1 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 and PGN-EDODM1; our ability to enroll patients in our clinical trials, including CONNECT1, CONNECT2, FREEDOM and FREEDOM2; that our interpretation of clinical and preclinical study results may be incorrect, or that we may not observe the levels of therapeutic activity in clinical testing that we anticipate based on prior clinical or preclinical results, including for PGN-EDO51 and PGN-EDODM1; our product candidates, including PGN-EDO51 and PGN-EDODM1, may not be safe and effective or otherwise demonstrate safety and efficacy in our clinical trials; adverse outcomes from our regulatory interactions, including delays in regulatory review, clearance to proceed or approval by regulatory authorities with respect to our programs, including clearance to commence planned clinical studies of our product candidates, or other regulatory feedback requiring modifications to our development programs, including in each case with respect to our CONNECT1, CONNECT2, FREEDOM and FREEDOM2 clinical trials; 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.
This release discusses PGN-EDO51 and PGN-EDODM1, investigational therapies that have not been approved for use in any country and is not intended to convey conclusions about their efficacy or safety. There is no guarantee that PGN-EDO51, PGN-EDODM1 or any other investigational therapy will successfully complete clinical development or gain regulatory authority approval.
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Investor Contact
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SVP, Investor Relations and Corporate Communications
dborah@pepgen.com
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Source: PepGen Inc.
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