Clinical and Immunological Results from Phase 1/2 Study of INO-3107 as a Treatment for Recurrent Respiratory Papillomatosis Published in Nature Communications
INOVIO (NASDAQ: INO) announced peer-reviewed data from its Phase 1/2 clinical trial of INO-3107 for treating recurrent respiratory papillomatosis (RRP) in Nature Communications. The trial demonstrated significant clinical benefits, with 81.3% (26/32) of patients requiring fewer surgeries post-treatment compared to the previous year. 28.1% (9/32) of patients achieved Complete Response, requiring no surgical intervention.
The treatment showed strong safety profile with only 41% reporting treatment-related adverse events, mostly mild injection site pain (31%) and fatigue (9%). INO-3107 induced lasting T cell responses specific to HPV-6 and HPV-11, with evidence of immune cells traveling to affected tissues.
INOVIO plans to submit its biologics license application (BLA) in mid-2025, seeking rolling submission and priority review. If approved, INO-3107 would become the first DNA medicine approved in the United States.
INOVIO (NASDAQ: INO) ha annunciato dati peer-reviewed dal suo trial clinico di Fase 1/2 per INO-3107 nel trattamento della papillomatosi respiratoria ricorrente (RRP) su Nature Communications. Lo studio ha dimostrato significativi benefici clinici, con l'81,3% (26/32) dei pazienti che ha richiesto meno interventi chirurgici dopo il trattamento rispetto all'anno precedente. Il 28,1% (9/32) dei pazienti ha raggiunto una Risposta Completa, senza necessità di intervento chirurgico.
Il trattamento ha mostrato un profilo di sicurezza robusto, con solo il 41% che ha riportato eventi avversi correlati al trattamento, per lo più lievi dolori nel sito di iniezione (31%) e affaticamento (9%). INO-3107 ha indotto risposte durevoli delle cellule T specifiche per HPV-6 e HPV-11, con evidenze di cellule immunitarie che si spostano nei tessuti colpiti.
INOVIO prevede di presentare la sua domanda di licenza biologica (BLA) a metà 2025, cercando una presentazione continua e una revisione prioritaria. Se approvato, INO-3107 diventerebbe il primo farmaco a base di DNA approvato negli Stati Uniti.
INOVIO (NASDAQ: INO) anunció datos revisados por pares de su ensayo clínico de Fase 1/2 sobre INO-3107 para el tratamiento de la papilomatosis respiratoria recurrente (RRP) en Nature Communications. El ensayo demostró beneficios clínicos significativos, con el 81,3% (26/32) de los pacientes que requirieron menos cirugías después del tratamiento en comparación con el año anterior. El 28,1% (9/32) de los pacientes logró una Respuesta Completa, sin necesidad de intervención quirúrgica.
El tratamiento mostró un fuerte perfil de seguridad, con solo el 41% reportando eventos adversos relacionados con el tratamiento, en su mayoría dolor leve en el sitio de inyección (31%) y fatiga (9%). INO-3107 indujo respuestas duraderas de células T específicas para HPV-6 y HPV-11, con evidencia de células inmunitarias viajando a los tejidos afectados.
INOVIO planea presentar su solicitud de licencia biológica (BLA) a mediados de 2025, buscando una presentación continua y revisión prioritaria. Si se aprueba, INO-3107 se convertiría en el primer medicamento de ADN aprobado en los Estados Unidos.
INOVIO (NASDAQ: INO)는 INO-3107의 재발성 호흡기 유두종증(RRP) 치료를 위한 1/2상 임상 시험에서 동료 검토된 데이터를 Nature Communications에 발표했습니다. 이 시험은 치료 후 81.3% (26/32)의 환자가 이전 해에 비해 수술 횟수를 줄였다는 중요한 임상적 이점을 보여주었습니다. 28.1% (9/32)의 환자가 수술적 개입 없이 완전 반응을 달성했습니다.
치료는 부작용이 발생한 환자가 41%에 불과하고, 대부분 경미한 주사 부위 통증(31%)과 피로(9%)로 나타나 강력한 안전성 프로필을 보여주었습니다. INO-3107은 HPV-6 및 HPV-11에 특이적인 지속적인 T 세포 반응을 유도하였으며, 면역 세포가 영향을 받은 조직으로 이동하는 증거가 있었습니다.
INOVIO는 2025년 중반에 생물학적 제제 면허 신청(BLA)을 제출할 계획이며, 연속 제출 및 우선 심사를 요청할 예정입니다. 승인될 경우 INO-3107은 미국에서 승인된 첫 번째 DNA 약물이 될 것입니다.
INOVIO (NASDAQ: INO) a annoncé des données évaluées par des pairs de son essai clinique de phase 1/2 concernant INO-3107 pour le traitement de la papillomatose respiratoire récurrente (RRP) dans Nature Communications. L'essai a démontré des avantages cliniques significatifs, avec 81,3% (26/32) des patients nécessitant moins de chirurgies après le traitement par rapport à l'année précédente. 28,1% (9/32) des patients ont atteint une Réponse Complète, sans intervention chirurgicale requise.
Le traitement a montré un bon profil de sécurité, avec seulement 41% des patients signalant des événements indésirables liés au traitement, principalement des douleurs légères au site d'injection (31%) et de la fatigue (9%). INO-3107 a induit des réponses durables des cellules T spécifiques à HPV-6 et HPV-11, avec des preuves de cellules immunitaires se déplaçant vers les tissus affectés.
INOVIO prévoit de soumettre sa demande de licence biologique (BLA) à la mi-2025, recherchant une soumission continue et un examen prioritaire. Si approuvé, INO-3107 deviendrait le premier médicament à ADN approuvé aux États-Unis.
INOVIO (NASDAQ: INO) hat peer-reviewed Daten aus seiner Phase 1/2 klinischen Studie zu INO-3107 zur Behandlung von wiederkehrender respiratorischer Papillomatose (RRP) in Nature Communications veröffentlicht. Die Studie zeigte signifikante klinische Vorteile, wobei 81,3% (26/32) der Patienten nach der Behandlung weniger Operationen benötigten als im Vorjahr. 28,1% (9/32) der Patienten erreichten eine vollständige Antwort, ohne chirurgische Intervention.
Die Behandlung wies ein starkes Sicherheitsprofil auf, da nur 41% behandlungsbedingte unerwünschte Ereignisse berichteten, hauptsächlich leichte Schmerzen an der Injektionsstelle (31%) und Müdigkeit (9%). INO-3107 induzierte anhaltende T-Zell-Antworten, die spezifisch für HPV-6 und HPV-11 sind, mit Beweisen dafür, dass Immunzellen in betroffene Gewebe wandern.
INOVIO plant, Mitte 2025 einen Antrag auf biologische Lizenz (BLA) einzureichen und strebt eine fortlaufende Einreichung und eine priorisierte Prüfung an. Wenn genehmigt, würde INO-3107 das erste in den Vereinigten Staaten zugelassene DNA-Medikament werden.
- 81.3% of patients showed reduced need for surgical interventions
- 28.1% of patients achieved Complete Response (no surgeries needed)
- 72% Overall Response Rate (Complete + Partial Response)
- Strong safety profile with no treatment-related AEs above Grade 2
- Demonstrated lasting T cell response through week 52
- BLA submission planned for mid-2025 with potential accelerated approval
- 19% of patients did not show reduction in surgical interventions
- 41% of patients experienced treatment-related adverse events
Insights
The Phase 1/2 trial results for INO-3107 published in Nature Communications present compelling evidence for INOVIO's DNA medicine approach in treating RRP. The 81.3% clinical response rate, with 28.1% of patients achieving complete response (no surgeries needed), represents a potentially transformative treatment option in a field where repeated surgeries are currently the only option.
The immunological data is particularly noteworthy. The demonstration of sustained T cell responses through 52 weeks, including both CD8+ cytotoxic T cells specific to HPV-6 and HPV-11, suggests robust and durable immune activation. The evidence of new clonal T cell populations infiltrating papilloma tissue in responders provides a clear mechanism of action linking the immunotherapy to clinical benefit.
The safety profile is remarkably clean, with only 41% of patients reporting treatment-related adverse events, mostly mild injection site reactions. This favorable tolerability, combined with the durability data showing continued improvement through years 2 and 3, positions INO-3107 as a potentially preferred treatment option.
The planned BLA submission in mid-2025, with requests for rolling submission and priority review, could represent a pivotal moment for both INOVIO and the broader DNA medicine field. If approved, INO-3107 would become the first DNA medicine approved in the United States, potentially validating INOVIO's platform technology and opening doors for applications in other indications.
Data shows that INO-3107 induced new populations of T cells in the blood that traveled to airway tissue and were associated with clinical benefit as measured by reduced need for surgeries
The Phase 1/2 study showed the majority of participants experienced a reduced need for surgery, providing great hope for RRP patients who face both risk of vocal cord damage and immense impact on their daily lives with every surgery," said Dr. Peter Belafsky, Director of the Center for Voice & Swallowing at UC Davis Health and a principal investigator on the trial. "INO-3107 was designed with those patient needs in mind and has the potential to transform the treatment paradigm for RRP."
Dr. Matthew Morrow, INOVIO's Vice President of Translational Science stated, "The combination of the full clinical data set and the immunological evaluation described in this publication allows for a complete view of the immunological impact of INO-3107, which is a compelling story of a T cell-based mechanism of action that drives clinical benefit. The publication describes in detail how INO-3107 engaged both the innate and adaptive arms of the immune system of treated patients and directly points to the emergence of new T cell populations after treatment that traveled to infected tissue to fight RRP."
"These important data characterizing the cytotoxic T cell-based mechanism of action of INO-3107, in conjunction with our recently reported durability data showing that clinical benefit continued to improve through year two and into year three after initial treatment, with half of patients not requiring any surgeries in year two, are part of the growing body of evidence that INO-3107 has the potential to be the preferred product of choice for both patients and healthcare providers," said Dr. Jacqueline Shea, INOVIO's CEO and President. "The primary goal for RRP patients is to reduce or eliminate the need for surgery and INO-3107 has the potential to do just that for the majority of patients. Every surgery matters and a safe and effective therapeutic alternative to surgery would be truly life-changing for RRP patients and their caregivers."
Highlights from the Nature Communications Paper
81.3% (26/32) of patients had a decrease of at least one surgical intervention from the prior year (defined as the Overall Clinical Response Rate) after INO-3107 administration, including28.1% (9/32) that required no surgical intervention (Complete Response) during or after the dosing window- The Overall Response Rate, which includes those patients who had either a Complete Response or a Partial Response (defined as ≥
50% reduction in surgeries) was72% - Patients in this trial were required to have ≥2 RRP surgical interventions in the year prior to initiating treatment
- The Overall Response Rate, which includes those patients who had either a Complete Response or a Partial Response (defined as ≥
- INO-3107 was well tolerated in the 32 patients enrolled:
41% (13/32) of patients reported a treatment-related Adverse Event (AE)- Most frequent treatment-related AEs reported were injection site pain (
31% ) and fatigue (9% ) - No treatment-related AEs greater than Grade 2 severity were reported
- INO-3107 induced T cell responses specific to HPV-6 and HPV-11, including cytotoxic CD8+ T cells, which were still present at week 52, indicating the establishment of a memory response
- INO-3107 expanded clonal T cell populations in peripheral blood, including induction of new clonal T cell populations that traveled to airway and papilloma tissue
- INO-3107 induced inflammatory responses in papilloma and airway tissue associated with antiviral activity, including:
- Interferon, cytokine and chemokine signaling
- Adaptive and innate immune cell infiltration, with emphasis on T cells
- TCR sequencing provided direct evidence of increased overall T cell infiltration compared to pre-treatment
- Cytotoxic T cell signatures were observed in T cell infiltrated papilloma/airway tissue
- T cell infiltration in airway tissues of clinical responders were predominantly new T cell clonal populations not detectable prior to INO-3107 treatment
- Enhanced T cell responses were observed in all patients, but there were differences in the T cell responses between responders and non-responders that were associated with clinical benefit among the responders
About RRP
RRP is a debilitating and rare disease caused primarily by HPV-6 and/or HPV-11. RRP is characterized by the development of small, wart-like growths, or papillomas, in the respiratory tract. While papillomas are generally benign, they can cause severe, life-threatening airway obstruction and respiratory complications. RRP can also significantly affect quality of life for patients by affecting the voice box, limiting the ability to speak effectively. Surgery to remove papillomas is the standard of care for RRP; however, the papillomas often grow back. INOVIO's market research to date with patients and healthcare professionals indicates that a reduction of even one surgery matters, because every surgery poses a significant risk of causing permanent damage to the vocal cords. The most widely cited
About INO-3107
INO-3107 is an investigational DNA medicine designed to elicit an antigen-specific T cell response against both HPV-6 and HPV-11 proteins. These targeted T cells seek out and kill HPV-6 and HPV-11 infected cells, with the aim of potentially preventing or slowing the growth of new papillomas. In a Phase 1/2 clinical trial conducted with INO-3107 in patients requiring ≥2 RRP surgical interventions in the year prior to initiating treatment,
The FDA previously granted INO-3107 Orphan Drug designation and Breakthrough Therapy designation and has advised INOVIO that it can submit a biologics license application under the FDA's accelerated approval program using data from INOVIO's already completed Phase 1/2 trial. The European Commission granted INO-3107 Orphan Drug designation. In addition, INOVIO has CE-marked its CELLECTRA® delivery device in the EU, which allows INOVIO to commercialize the device in the EU and other geographies that recognize CE-marking. The
About INOVIO's DNA Medicines Platform
INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's proprietary CELLECTRA® delivery devices are designed to optimally deliver its DNA medicines to the body's cells without requiring chemical adjuvants or lipid nanoparticles and without the risk of the anti-vector response historically seen with viral vector platforms.
About INOVIO
INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com.
Forward-Looking Statements
This press release contains certain forward-looking statements relating to our business, including the planned submission of a BLA in mid-2025 and plan to request rolling submission and priority review under the FDA's accelerated approval program, and the potential clinical benefit of INO-3107 if approved. Actual events or results may differ from the expectations set forth herein as a result of a number of factors, including uncertainties inherent in pre-clinical studies, clinical trials, product development programs and commercialization activities and outcomes, the availability of funding to support continuing research and studies in an effort to prove safety and efficacy of electroporation technology as a delivery mechanism or develop viable DNA medicines, our ability to support our pipeline of DNA medicine products, the ability of our collaborators to attain development and commercial milestones for products we license and product sales that will enable us to receive future payments and royalties, the adequacy of our capital resources, the availability or potential availability of alternative therapies or treatments for the conditions targeted by us or collaborators, including alternatives that may be more efficacious or cost effective than any therapy or treatment that we and our collaborators hope to develop, issues involving product liability, issues involving patents and whether they or licenses to them will provide us with meaningful protection from others using the covered technologies, whether such proprietary rights are enforceable or defensible or infringe or allegedly infringe on rights of others or can withstand claims of invalidity and whether we can finance or devote other significant resources that may be necessary to prosecute, protect or defend them, the level of corporate expenditures, assessments of our technology by potential corporate or other partners or collaborators, capital market conditions, the impact of government healthcare proposals and other factors set forth in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, and other filings we make from time to time with the Securities and Exchange Commission. There can be no assurance that any product candidate in our pipeline will be successfully developed, manufactured, or commercialized, that the results of clinical trials will be supportive of regulatory approvals required to market products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and we undertake no obligation to update or revise these statements, except as may be required by law.
Contacts
Media: Jennie Willson (267) 429-8567 communications@inovio.com
Investors: Peter Vozzo, ICR Healthcare, 443-213-0505 investor.relations@inovio.com
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SOURCE INOVIO Pharmaceuticals, Inc.
FAQ
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