Vaccinex to Report Promising New Clinical Data Revealing Pepinemab’s Unique Mechanism to Enhance Immunotherapy at Annual Meeting of American Association for Cancer Research (AACR)
Vaccinex (NASDAQ: VCNX) announced new clinical data demonstrating pepinemab's mechanism in enhancing immunotherapy effectiveness, to be presented at the 2025 AACR Annual Meeting in Chicago on April 29, 2025.
The data reveals that pepinemab, a Semaphorin 4D blocking immunotherapy, induces mature lymphoid structures (TLS) that correlate with durable clinical benefits in both metastatic melanoma and head and neck cancer patients. By blocking SEMA4D inhibitory signals to Dendritic Cells, pepinemab enables coordinated immune cell interactions within TLS, amplifying mature T cell responses.
Key findings show pepinemab's ability to transform immunologically 'cold' tumors into 'hot' immune centers in HPV-negative and PD-L1-low head and neck cancer. In melanoma patients, neoadjuvant treatment with pepinemab enhanced TLS maturity and correlated with longer recurrence-free survival when combined with immune checkpoint inhibitors.
Vaccinex (NASDAQ: VCNX) ha annunciato nuovi dati clinici che dimostrano il meccanismo di pepinemab nel potenziare l'efficacia dell'immunoterapia, dati che saranno presentati al 2025 AACR Annual Meeting a Chicago il 29 aprile 2025.
I dati mostrano che pepinemab, un'immunoterapia che blocca la Semaforina 4D, induce la formazione di strutture linfatiche mature (TLS) correlate a benefici clinici duraturi sia nei pazienti con melanoma metastatico sia in quelli con tumore della testa e del collo. Bloccando i segnali inibitori di SEMA4D verso le cellule dendritiche, pepinemab favorisce interazioni coordinate tra cellule immunitarie all'interno delle TLS, amplificando le risposte delle cellule T mature.
I risultati principali evidenziano la capacità di pepinemab di trasformare tumori immunologicamente “freddi” in centri immunitari “caldi” nei tumori della testa e del collo HPV-negativi e a basso livello di PD-L1. Nei pazienti con melanoma, il trattamento neoadiuvante con pepinemab ha migliorato la maturità delle TLS e si è correlato a una maggiore sopravvivenza libera da recidive quando combinato con inibitori dei checkpoint immunitari.
Vaccinex (NASDAQ: VCNX) anunció nuevos datos clínicos que demuestran el mecanismo de pepinemab para mejorar la eficacia de la inmunoterapia, que serán presentados en la Reunión Anual 2025 de AACR en Chicago el 29 de abril de 2025.
Los datos revelan que pepinemab, una inmunoterapia que bloquea la Semaforina 4D, induce la formación de estructuras linfoides maduras (TLS) que se correlacionan con beneficios clínicos duraderos tanto en pacientes con melanoma metastásico como con cáncer de cabeza y cuello. Al bloquear las señales inhibitorias de SEMA4D hacia las células dendríticas, pepinemab permite interacciones coordinadas entre células inmunitarias dentro de las TLS, amplificando las respuestas de células T maduras.
Los hallazgos clave muestran la capacidad de pepinemab para transformar tumores inmunológicamente “fríos” en centros inmunitarios “calientes” en cáncer de cabeza y cuello HPV-negativo y con bajo nivel de PD-L1. En pacientes con melanoma, el tratamiento neoadyuvante con pepinemab mejoró la madurez de las TLS y se asoció con una mayor supervivencia libre de recurrencia cuando se combinó con inhibidores de puntos de control inmunitarios.
Vaccinex (NASDAQ: VCNX)는 펩시네맙의 면역치료 효과 증진 기전을 입증하는 새로운 임상 데이터를 발표했으며, 해당 데이터는 2025년 4월 29일 시카고에서 열리는 2025 AACR 연례회의에서 발표될 예정입니다.
데이터에 따르면, 세마포린 4D 차단 면역치료제인 펩시네맙은 전이성 흑색종 및 두경부암 환자에서 내구성 임상 이익과 연관된 성숙 림프구 구조(TLS)를 유도합니다. SEMA4D의 수지상세포에 대한 억제 신호를 차단함으로써, 펩시네맙은 TLS 내에서 면역 세포 간의 조율된 상호작용을 가능하게 하여 성숙 T세포 반응을 증폭시킵니다.
주요 결과는 펩시네맙이 HPV 음성 및 PD-L1 낮은 두경부암에서 면역학적으로 ‘냉담한’ 종양을 ‘뜨거운’ 면역 중심으로 전환하는 능력을 보여줍니다. 흑색종 환자에서는 펩시네맙의 신보조요법이 TLS 성숙도를 향상시켰고, 면역관문억제제와 병용 시 재발 없는 생존 기간 연장과 연관되었습니다.
Vaccinex (NASDAQ : VCNX) a annoncé de nouvelles données cliniques démontrant le mécanisme de pepinemab pour améliorer l'efficacité de l'immunothérapie, qui seront présentées lors de la réunion annuelle AACR 2025 à Chicago le 29 avril 2025.
Les données révèlent que pepinemab, une immunothérapie bloquant la Sémaphorine 4D, induit des structures lymphoïdes matures (TLS) corrélées à des bénéfices cliniques durables chez les patients atteints de mélanome métastatique et de cancers de la tête et du cou. En bloquant les signaux inhibiteurs de SEMA4D vers les cellules dendritiques, pepinemab permet des interactions coordonnées entre les cellules immunitaires au sein des TLS, amplifiant les réponses des lymphocytes T matures.
Les résultats clés montrent la capacité de pepinemab à transformer les tumeurs immunologiquement « froides » en centres immunitaires « chauds » dans les cancers de la tête et du cou HPV-négatifs et à faible expression de PD-L1. Chez les patients atteints de mélanome, le traitement néoadjuvant par pepinemab a amélioré la maturité des TLS et a été corrélé à une survie sans récidive prolongée lorsqu'il est combiné avec des inhibiteurs de points de contrôle immunitaires.
Vaccinex (NASDAQ: VCNX) gab neue klinische Daten bekannt, die den Wirkmechanismus von Pepinemab zur Steigerung der Wirksamkeit von Immuntherapien belegen. Diese Daten werden auf dem AACR-Jahrestreffen 2025 in Chicago am 29. April 2025 vorgestellt.
Die Daten zeigen, dass Pepinemab, eine Immuntherapie, die Semaphorin 4D blockiert, die Bildung reifer lymphoider Strukturen (TLS) induziert, die mit nachhaltigen klinischen Vorteilen bei Patienten mit metastasiertem Melanom und Kopf-Hals-Tumoren korrelieren. Durch die Blockade der hemmenden SEMA4D-Signale an dendritische Zellen ermöglicht Pepinemab koordinierte Immunzell-Interaktionen innerhalb der TLS und verstärkt die Reaktionen reifer T-Zellen.
Wesentliche Erkenntnisse zeigen die Fähigkeit von Pepinemab, immunologisch „kalte“ Tumoren bei HPV-negativen und PD-L1-niedrigen Kopf-Hals-Tumoren in „heiße“ Immunzentren zu verwandeln. Bei Melanompatienten verbesserte die neoadjuvante Behandlung mit Pepinemab die Reife der TLS und korrelierte mit einer längeren rezidivfreien Überlebenszeit in Kombination mit Immun-Checkpoint-Inhibitoren.
- Demonstrated longer recurrence-free survival in melanoma patients
- Successfully converts 'cold' tumors to 'hot' immune centers in head and neck cancer
- Shows effectiveness in enhancing immunotherapy response
- Proves mechanism of action through TLS formation and maturity
- Results are still in clinical trial phase, pending full approval
- data on long-term efficacy and safety
- Many patients still progress despite initial benefits from checkpoint inhibitors
Insights
Pepinemab demonstrates promising mechanism enhancing immunotherapy efficacy through tertiary lymphoid structure formation in tough-to-treat cancers.
Vaccinex's upcoming AACR presentation reveals significant insights into how pepinemab enhances immunotherapy effectiveness. The data demonstrates that by blocking Semaphorin 4D (SEMA4D), pepinemab enables productive interactions between T cells and dendritic cells within tertiary lymphoid structures (TLS) – organized immune centers within tumors that amplify anti-cancer responses.
What's particularly noteworthy is pepinemab's ability to induce these TLS in immunologically "cold" tumors that typically resist treatment, including HPV-negative and PD-L1-low head and neck cancers. This transformation from "cold" to "hot" tumors represents a critical advancement in addressing a major limitation of current immunotherapies.
The clinical correlation data showing enhanced TLS maturity associated with longer recurrence-free survival in melanoma patients is especially promising. While many patients initially respond to checkpoint inhibitors, progression frequently occurs. Pepinemab's mechanism addresses this challenge through immune microenvironment modulation.
The neoadjuvant setting (pre-surgery treatment) being explored for this combination approach is particularly strategic, as it can potentially prime the immune system when tumor burden is lower and immune function less compromised. The mechanism's ability to regulate dendritic cell function – essential mediators of T cell activation – provides a strong biological rationale for pepinemab's observed effects.
Vaccinex's revelations about pepinemab represent a strategic advancement in their clinical program. By demonstrating a clear mechanism of action through SEMA4D inhibition, the company establishes scientific credibility for their approach in the competitive immuno-oncology landscape.
The data positioning pepinemab as a potential combination enhancer for checkpoint inhibitors addresses a significant market need. Despite the success of immunotherapies like pembrolizumab and nivolumab, response rates remain to 20-40% in many cancer types. Agents that can extend these benefits to non-responders have considerable clinical and commercial potential.
For pepinemab, the ability to induce tertiary lymphoid structures provides a differentiated mechanism from other immunotherapy combination approaches. The correlation between TLS formation and improved clinical outcomes strengthens the scientific rationale for continued development.
The dual presentations at AACR examining both the fundamental mechanism and clinical correlations indicate a comprehensive translational approach. This strategy of connecting mechanism to outcomes is particularly valuable for attracting potential partners and supporting future clinical development.
The ongoing evaluation in head and neck cancer, with additional data expected this spring, suggests a focused clinical development plan targeting indications where the TLS-inducing mechanism could provide meaningful benefit. For Vaccinex, these positive signals in the pepinemab program represent important progress for their lead asset.
Neoadjuvant treatment with pepinemab appears to induce abundant, mature lymphoid structures that correlate with durable clinical benefit of immunotherapy in patients with metastatic melanoma.
Pepinemab, Semaphorin 4D blocking immunotherapy, also appears to induce the formation of efficient lymphoid structures in “cold” tumors of patients with recurrent and metastatic head and neck cancer.
ROCHESTER, N.Y., April 21, 2025 (GLOBE NEWSWIRE) -- Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and Alzheimer’s disease (AD) through the inhibition of Semaphorin 4D (SEMA4D), today announced that it will present exciting new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies, corresponding with improved survival benefit in patients with melanoma and head and neck cancer at the 2025 Annual Meeting of American Association for Cancer Research (AACR) in Chicago on April 29, 2025. Elizabeth Evans, PhD, Senior VP Discovery and Translational Medicine, will present results of these studies in two presentations.
| AACR Conference Information: | ||
| Date: | Tuesday, April 29, 2025 | |
| Presentation title: | Regulating dendritic cells to promote mature tertiary lymphoid structures and enhance anti-tumor immunity. Presentation #3975 | |
| Time: | 9-12 AM CDT/10 AM – 1 PM EDT. | |
| Session Title: | The Tumor Immune Interplay as a Driver of Progression | |
| Presentation title: | Neoadjuvant pepinemab enhances DC function associated with mature tertiary lymphoid structures and activity of immune checkpoint blockade in patients with metastatic melanoma. Presentation #6007 | |
| Time: | 2-5 PM CDT/ 3-6 PM EDT. | |
| Session Title: | Therapeutic Antibodies, Including Engineered Antibodies 2 | |
| Access: | Posters will be presented in-person on Tuesday, April 29 at McCormick Place Convention Center, Chicago, Illinois, and on AACR 2025 virtual meeting platform at 1:00 PM ET on Friday, April 25, 2025. | |
Previously reported data from these two clinical studies suggest a crucial role of pepinemab to facilitate immune cell interactions within highly organized and robust centers of immunity, called tertiary lymphoid structures, or TLS. By blocking the SEMA4D inhibitory signal to Dendritic Cells (DC), pepinemab allows productive, coordinated interactions between SEMA4D+ T cells, key effector cells capable of eradicating tumors, and DC, regulatory cells that promote immune cell interactions within TLS so as to amplify mature T cell responses. New data will characterize clinical outcomes, biomarkers, and mechanisms of these interactions in patients treated with pepinemab in combination with immune checkpoint therapy.
Boosting TLS within tumors is an area of growing excitement because the presence of TLS has been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. A limitation in the field has been identification of safe and effective therapies that can induce formation and harness the potential of TLS to enable durable benefit to patients. Pepinemab may represent a solution to this problem, as our data demonstrate the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative and PD-L1-low head and neck cancer, into hot immune centers by inducing robust and mature TLS.
Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various cancers, showing improved immune and clinical benefit in the preoperative setting compared to standard post surgery adjuvant treatments. Despite these advances, many patients who initially benefit from antibodies that block inhibitory checkpoint molecules (e.g. PD-1, CTLA 4) will progress. More effective combination therapies are needed. Neoadjuvant treatment with pepinemab enhanced TLS maturity and correlated with longer recurrence-free survival when combined with immune checkpoint inhibitors in patients with metastatic melanoma. Evaluation of pepinemab in the neoadjuvant setting for patients with head and neck cancer is ongoing and will be reported at upcoming scientific meeting this Spring.
About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind to plexin-B1 receptors to trigger collapse of the actin cytoskeleton in cells and lead to loss of homeostatic functions of dendritic cells in immune tissue and of astrocytes and other glial cells in the brain. Pepinemab appears to be well-tolerated with a favorable safety profile in multiple clinical trials in different cancer and neurological indications.
About Vaccinex Inc.
Vaccinex, Inc. is pioneering a differentiated approach to treating slowly progressive neurodegenerative diseases and cancer through the inhibition of semaphorin 4D (SEMA4D). The Company’s lead drug candidate, pepinemab, blocks SEMA4D, a potent biological effector that it believes prevents infiltration and activation of immune cells in tumors and triggers damaging inflammation in neurodegenerative diseases. In oncology, pepinemab is being evaluated in combination with KEYTRUDA® in the Phase 1b/2 KEYNOTE-B84 study in recurrent or metastatic head and neck cancer (HNSCC) and in combination with BAVENCIO® in a Phase 1b/2 study in patients with metastatic pancreatic adenocarcinoma (PDAC). The oncology clinical program also includes several investigator-sponsored studies in solid tumors including breast cancer and melanoma. We believe pepinemab has also given promising results as a monotherapy in the Phase 1b/2 SIGNAL-AD study in Alzheimer’s Disease, and the Company has previously published promising Phase 2 data suggesting a slowing of cognitive decline in Huntington’s disease.
Vaccinex has global commercial and development rights to pepinemab and is the sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Additional information about the study is available at: clinicaltrials.gov.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. BAVENCIO®/avelumab is provided by Merck KGaA, Darmstadt, Germany, previously as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer.
Forward Looking Statements
To the extent that statements contained in this press release are not descriptions of historical facts regarding Vaccinex, Inc. (“Vaccinex,” “we,” “us,” or “our”), they are forward-looking statements reflecting management’s current beliefs and expectations. Such statements include, but are not limited to, statements about our plans, expectations and objectives with respect to the results and timing of the SIGNAL-AD and KEYNOTE-B84 clinical trials; the use and potential benefits of pepinemab in R/M HNSCC, lung cancer, metastatic pancreatic adenocarcinoma (PDAC) and other indications; the potential for benefits as compared to single agent KEYTRUDA® or BAVENCIO®; expectations with respect to the collaboration of Merck,; and other statements identified by words such as “anticipate,” “believe,” “plans,” “schedule,” “being,” “will,” “appears,” “expect,” “ongoing,” “potential,” “promising,” “suggest”, and similar expressions or their negatives (as well as other words and expressions referencing future events, conditions, or circumstances). Forward-looking statements involve substantial risks and uncertainties that could cause the outcome of our research and pre-clinical development programs, clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, uncertainties inherent in the execution, cost and completion of preclinical studies and clinical trials, that interim and preliminary data may not be predictive of final results and does not ensure success in later clinical trials, uncertainties related to regulatory approval, risks related to our dependence on our lead product candidate pepinemab, and other matters that could affect our development plans or the commercial potential of our product candidates. Except as required by law, the Company assumes no obligation to update these forward-looking statements. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, see the section titled “Risk Factors” in our previous reports filed with the Securities and Exchange Commission and the other risks and uncertainties described in the Company’s annual year-end Form 10-K filed with the SEC.
Investor Contact
Elizabeth Evans, PhD
Senior Vice President, Vaccinex, Inc.
(585) 271-2700
eevans@vaccinex.com
FAQ
What are the key findings of Vaccinex's (VCNX) pepinemab clinical trials in cancer treatment?
How does pepinemab's mechanism of action work in cancer treatment?
What are the presentation details for VCNX's pepinemab data at AACR 2025?
What is pepinemab's effect on 'cold' tumors in head and neck cancer?
