Immunology Data Shows INOVIO's INO-3107 Induced Expansion of New Clonal T Cells That Infiltrate Airway Tissue and Correspond With Reduction of Surgeries for RRP Patients Observed in Phase 1/2 Trial
INOVIO announced new immunology data supporting the clinical activity of INO-3107 in treating recurrent respiratory papillomatosis (RRP). The data shows INO-3107 induced expansion of new clonal T cells in blood that weren't detectable before treatment. These cells traveled to papilloma and airway tissues, generating an inflammatory and anti-viral response consistent with reduced surgery needs for RRP patients with HPV-6 and HPV-11. The Phase 1/2 trial's immunological testing demonstrated the drug's ability to induce T cell responses specific to HPV-6 and HPV-11, including cytotoxic CD8+ T cells present at week 52, indicating memory response establishment.
INOVIO ha annunciato nuovi dati immunologici che supportano l'attività clinica di INO-3107 nel trattamento della papillomatosi respiratoria ricorrente (RRP). I dati mostrano che INO-3107 ha indotto l'espansione di nuove cellule T clonali nel sangue che non erano rilevabili prima del trattamento. Queste cellule si sono spostate verso i tessuti papilloma e delle vie aeree, generando una risposta infiammatoria e antivirale coerente con la riduzione della necessità di interventi chirurgici per i pazienti RRP affetti da HPV-6 e HPV-11. I test immunologici dello studio di Fase 1/2 hanno dimostrato la capacità del farmaco di indurre risposte delle cellule T specifiche per HPV-6 e HPV-11, comprese le cellule T citotossiche CD8+ presenti alla settimana 52, indicando l'instaurazione di una risposta di memoria.
INOVIO anunció nuevos datos de inmunología que respaldan la actividad clínica de INO-3107 en el tratamiento de la papillomatosis respiratoria recurrente (RRP). Los datos muestran que INO-3107 indujo la expansión de nuevas células T clonales en sangre que no eran detectables antes del tratamiento. Estas células viajaron a los tejidos de los papilomas y de las vías respiratorias, generando una respuesta inflamatoria y antiviral consistente con la reducción de las necesidades quirúrgicas para los pacientes con RRP que tienen HPV-6 y HPV-11. Las pruebas inmunológicas del ensayo de Fase 1/2 demostraron la capacidad del fármaco para inducir respuestas de células T específicas para HPV-6 y HPV-11, incluidas las células T citotóxicas CD8+ presentes en la semana 52, lo que indica el establecimiento de una respuesta de memoria.
INOVIO는 재발성 호흡기 유두종증 (RRP) 치료를 위한 INO-3107의 임상 활동을 뒷받침하는 새로운 면역학적 데이터를 발표했습니다. 데이터에 따르면, INO-3107은 치료 전에는 감지되지 않았던 혈액에서 새로운 클론 T세포의 확장을 유도했습니다. 이러한 세포는 유두종 및 기도 조직으로 이동하여, HPV-6 및 HPV-11 환자들의 RRP에 대한 수술 필요성을 줄이는 것과 일치하는 염증 및 항바이러스 반응을 생성했습니다. 1/2상 시험의 면역학적 테스트는 이 약물이 HPV-6 및 HPV-11에 특이적인 T세포 반응을 유도하는 능력을 보여주었으며, 52주차에 존재하는 세포독성 CD8+ T세포가 이러한 기억 반응의 형성을 나타냅니다.
INOVIO a annoncé de nouvelles données immunologiques soutenant l'activité clinique de INO-3107 dans le traitement de la papillomatose respiratoire récurrente (RRP). Les données montrent qu'INO-3107 a induit l'expansion de nouvelles cellules T clonales dans le sang qui n'étaient pas détectables avant le traitement. Ces cellules ont migré vers les tissus papillomateux et des voies respiratoires, générant une réponse inflammatoire et antivirale cohérente avec une réduction des besoins chirurgicaux pour les patients RRP porteurs de HPV-6 et HPV-11. Les tests immunologiques de l'essai de Phase 1/2 ont démontré la capacité du médicament à induire des réponses des cellules T spécifiques pour HPV-6 et HPV-11, y compris des cellules T cytotoxiques CD8+ présentes à la semaine 52, ce qui indique l'établissement d'une réponse de mémoire.
INOVIO hat neue immunologische Daten bekannt gegeben, die die klinische Aktivität von INO-3107 bei der Behandlung von wiederkehrender respiratorischer Papillomatose (RRP) unterstützen. Die Daten zeigen, dass INO-3107 die Expansion neuer klonaler T-Zellen im Blut induzierte, die vor der Behandlung nicht nachweisbar waren. Diese Zellen wanderten in die Papillom- und Atemweggewebe und erzeugten eine entzündliche und antivirale Reaktion, die mit einem verringerten chirurgischen Bedarf bei RRP-Patienten mit HPV-6 und HPV-11 übereinstimmt. Die immunologischen Tests der Phase 1/2-Studie zeigten die Fähigkeit des Medikaments, spezifische T-Zell-Antworten auf HPV-6 und HPV-11 auszulösen, einschließlich cytotoxischer CD8+ T-Zellen, die in Woche 52 vorhanden waren, was auf die Etablierung einer Gedächtnisantwort hinweist.
- INO-3107 showed clinical efficacy in reducing surgeries for RRP patients
- Drug demonstrated sustained immune response with T cells present at week 52
- Treatment successfully induced antigen-specific immune responses against target HPV strains
- Clinical activity maintained despite immunosuppressive conditions
- None.
Insights
The immunology data for INO-3107 represents a significant scientific breakthrough in RRP treatment. The study demonstrates three key findings:
- Generation of new clonal T cells specifically targeting HPV-6 and HPV-11
- Successful migration of these T cells to papilloma sites
- Sustained immune response lasting through week 52
Particularly noteworthy is the ability to overcome the immunosuppressive tumor microenvironment, a common challenge in immunotherapy. The presence of cytotoxic CD8+ T cells and inflammatory markers indicates robust immune activation, correlating with reduced surgical interventions. This mechanism validation strengthens INO-3107's potential as a transformative therapy for RRP patients who currently rely on repeated surgeries.
From a market perspective, this data significantly de-risks INO-3107's development program. The detailed mechanism validation addresses a critical concern for DNA medicines - demonstrating clear biological activity. For INOVIO, success in RRP could validate their broader DNA medicine platform, potentially increasing investor confidence in their pipeline. The RRP market, while niche, represents a high-unmet need with recurring treatment costs. A therapy reducing surgical interventions could command premium pricing, particularly given the strong efficacy data and sustained response through 52 weeks.
- New immunology data shows INO-3107 induced an expansion of new clonal T cells in blood that were not detectable prior to treatment
- New clonal T cells in the blood travelled to papilloma and airway tissues and generated an inflammatory and anti-viral response consistent with a reduced need for surgeries for patients with recurrent respiratory papillomatosis (RRP) caused by HPV-6 and HPV-11
- Data supporting mechanism of action for INO-3107 to be presented at 36th International Papillomavirus Conference in
Edinburgh, UK
"These new immunology data are consistent with the clinical effect observed in our Phase 1/2 trial of elimination or reduction in the incidence of papilloma in the airway of RRP patients," said Dr. Matthew Morrow, INOVIO's Vice President of Translational Sciences. "In a thorough immunological assessment, we observed that T cell infiltration in airway tissues of clinical responders was predominantly comprised of a T cell population detectable only after administration of INO-3107. This evidence supports the mechanism of action of INO-3107 and its ability to induce antigen-specific cytotoxic T cells targeting HPV-6 and HPV-11. Furthermore, this data adds to the body of evidence indicating that DNA medicines are an effective CD8 T cell generating platform."
Bettie M. Steinberg, Interim Dean and Professor, Elmezzi Graduate School of Molecular Medicine, Northwell Health, said, "This is very encouraging data. Not only did most patients improve clinically with INO 3107 treatment, but the induction of a systemic inflammatory T-cell response and new T-cell clones that travel to the papilloma tissue to contribute to a cytotoxic response shows that it is possible to effectively address the immune dysregulation against HPV that is a hallmark of RRP."
Summary of Immunology Data
The new immunology data is to be presented at the 36th International Papillomavirus Conference (November 12-15). It builds on data presented at the American Association for Cancer Research (AACR) Special Conference on October 19. Collectively, these immunology data provide further support of INO-3107's ability to induce antigen-specific T cell responses against HPV-6 and HPV-11 and drive recruitment of T cells into papilloma and airway tissues of RRP patients, which could potentially slow or eliminate papilloma regrowth.
INOVIO conducted a number of immunological assessments on blood samples taken throughout the trial and tissue samples taken at the beginning and end of its 52-week Phase 1/2 trial involving 32 adult RRP patients. The immunological testing showed INO-3107 produced:
- Induction of T cell responses specific for HPV-6 and HPV-11, including cytotoxic CD8+ T cells still present at week 52, indicating an establishment of memory response
- Expansion of new clonal T cell populations in peripheral blood that travel to papilloma or airway tissues
- Induction of inflammatory responses in papilloma and airway tissue, including:
- Interferon, cytokine and chemokine signaling
- Adaptive and innate immune cell infiltration, with emphasis on T cells
- Cytotoxic signatures of infiltrated T cells in papilloma/airway tissue, and direct evidence of increased overall T cell infiltration compared to pre-treatment
- Clinical activity not impacted by immunosuppressive papilloma microenvironment
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 are designed to 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,
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 our plans to develop and commercialize DNA medicines and expectations regarding our research and development programs, including timelines and prospects for regulatory approval, expectations regarding INO-3107's ability to maintain T cell response and overall efficacy, as well as benefits for patients. 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 June 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 jennie.willson@inovio.com
Investors: Thomas Hong (267) 440-4298 thomas.hong@inovio.com
View original content to download multimedia:https://www.prnewswire.com/news-releases/immunology-data-shows-inovios-ino-3107-induced-expansion-of-new-clonal-t-cells-that-infiltrate-airway-tissue-and-correspond-with-reduction-of-surgeries-for-rrp-patients-observed-in-phase-12-trial-302303842.html
SOURCE INOVIO Pharmaceuticals, Inc.
FAQ
What are the key findings of INOVIO's INO-3107 immunology data in 2024?
How long did the Phase 1/2 trial for INO-3107 last?
What type of immune response did INO-3107 generate in RRP patients?
Where will INOVIO present the new INO-3107 immunology data?
