BNT113 / BioNTech - LARVOL DELTA

Translational Challenges and Opportunities in mRNA Cancer Vaccines. (PubMed, Cancer Discov) - "Messenger RNA (mRNA) cancer vaccines have progressed rapidly, with personalized platforms such as mRNA-4157 and BNT122 demonstrating feasibility, safety, and durable immune activity but limited scalability. Off-the-shelf constructs, including BNT111 and BNT113, enable faster, broader deployment, yet they risk reduced precision or immune tolerance...This mini-review synthesizes emerging clinical evidence and outlines strategies such as modular vaccine design, prime-boost vaccination regimens, and adaptive trial frameworks to reconcile these trade-offs and advance scalable, durable mRNA vaccines for broad oncologic impact. By dissecting the competing design pressures that shape mRNA vaccine performance, this mini-review proposes integrative strategies, spanning modular architectures, prime-boost regimens, and adaptive trials, to reconcile immunologic potency with manufacturability and safety, charting a roadmap toward next-generation cancer vaccines."

Journal • Review • Oncology

AHEAD-MERIT: A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 (clinicaltrials.gov) - P2/3 | N=350 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Apr 2029 ➔ Aug 2028 | Trial primary completion date: Apr 2029 ➔ Aug 2028

Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

AHEAD-MERIT: A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 (clinicaltrials.gov) - P2/3 | N=358 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

mRNA Vaccines Targeting HPV E6/E7: A New Frontier in Cervical Cancer Immunotherapy. (PubMed, Crit Rev Oncol Hematol) - "Recent clinical progress, including BioNTech's BNT113 vaccine which received FDA Fast Track designation for HPV16-positive head and neck cancer, is discussed alongside ongoing challenges in delivery optimization, tumor microenvironment immunosuppression, and manufacturing scalability. The review concludes with future perspectives on combination strategies with immune checkpoint inhibitors and the potential for personalized neoantigen approaches."

Journal • Review • Cervical Cancer • Head and Neck Cancer • Human Papillomavirus Infection • Infectious Disease • Oncology • Solid Tumor

A novel mRNA-based therapeutic vaccine elicits robust anti-tumor immunity against HPV-associated malignancies. (PubMed, Front Immunol) - "In this study, we developed TriStim-E6/E7, a novel HPV mRNA vaccine that combines E6/E7 antigens with three T cell co-stimulatory molecules (CD80, 4-1BBL, and CD70)...Additionally, a "cytokine release storm" experiment using PBMC-reconstituted mice confirmed a favorable safety profile of TriStim-E6/E7 mRNA. These findings collectively demonstrate the promising therapeutic potential of TriStim-E6/E7 mRNA for clinical translation against HPV-associated malignancies."

Journal • Human Papillomavirus Infection • Infectious Disease • Oncology • CD27 • CD4 • CD70 • CD8 • CD80

Personalized and HPV cancer vaccines in head and neck squamous cell carcinoma: from concept to clinical implementation. (PubMed, Transl Oncol) - "Compounds such as TG4050, mRNA-4157, and PGV001 have shown early, hypothesis-generating signals of activity (from small early-phase studies), particularly in the adjuvant setting. HPV-targeted vaccines, including PDS0101, BNT113, and CUE-101, are being explored in HPV-positive HNSCC, mainly in combination with ICIs...The greatest clinical potential of therapeutic vaccination may lie in earlier disease stages, where the tumor burden is lower and immune modulation more feasible. Further clinical and translational research is needed to define the optimal integration of vaccine-based therapies into multimodal treatment paradigms for HNSCC."

IO biomarker • Journal • Review • Head and Neck Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

AHEAD-MERIT: A Phase II/III Trial of First Line (1L) BNT113 plus Pembrolizumab in Unresectable Recurrent or Metastatic HPV16+ HNSCC (MHNCS 2026) - P2/3 | "TBD"

Clinical • IO biomarker • Metastases • P2/3 data • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

BioNTech Receives FDA Fast Track Designation for mRNA Cancer Immunotherapy Candidate BNT113 in HPV16+ Head and Neck Cancer (BioNTech Press Release) - "The designation has been granted based on preliminary safety and efficacy data from the ongoing pivotal Phase 2/3 AHEAD-MERIT clinical trial (NCT04534205) evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ HNSCC expressing PD-L1."

Fast track • Squamous Cell Carcinoma of Head and Neck

BioNTech Provides Strategic Business Update and Outlines 2026 Areas of Focus at 44th Annual J.P. Morgan Healthcare Conference (The Manila Times) - "Expected 2026 oncology milestones include seven late-stage data readouts...Additional late-stage trial readouts through 2030+ set to create multiple launch opportunities across tumor types, building BioNTech into a multi-product oncology company."

Clinical data • New P3 trial • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

AHEAD-MERIT: A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 (clinicaltrials.gov) - P2/3 | N=350 | Recruiting | Sponsor: BioNTech SE | Phase classification: P2 ➔ P2/3 | Trial completion date: May 2028 ➔ Apr 2029 | Trial primary completion date: May 2028 ➔ Apr 2029

Phase classification • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Synergy Effects of HPV E6-E7 Encoding mRNA and Nucleic Acid Immunostimulators Improve Therapeutic Potential in TC-1 Graft Tumor. (PubMed, J Med Virol) - "In TC-1 tumor-bearing mice, the subcutaneous immunization of LNP-CPG 1018 capsulated HPV E6-E7 mRNA elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In conclusion, the LNP-CPG 1018 system is a promising delivery platform for facilitating the development of HPV E6-E7 mRNA cancer vaccines."

Journal • Cervical Cancer • Human Papillomavirus Infection • Infectious Disease • Oncology • Solid Tumor

Exploratory efficacy and translational results from the safety run in of AHEAD-MERIT, a phase II trial of first line pembrolizumab plus the fixed-antigen cancer vaccine BNT113 in advanced HPV16+ HNSCC (ESMO 2024) - P2 | "BNT113 + pembrolizumab was well tolerated, showed encouraging signs of efficacy, and the RP2D was confirmed. We will present serum cytokine and T cell profiling data."

Clinical • IO biomarker • Metastases • P2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • CD8 • PD-L1

Observational study on the correlation between the immune response of patients' peripheral blood stimulated by therapeutic HPV mRNA vaccine in vitro and the pathological results and clinical prognosis of patients (ChiCTR) - P=N/A | N=150 | Not yet recruiting | Sponsor: Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine; Renji Hospital affiliated to Shanghai Jiaotong University School of Medi

New trial

HARE-40: A phase I/II trial of therapeutic HPV vaccine (BNT113) in patients with HPV16 driven carcinoma (ESMO 2024) - P=N/A | "BNT113 was overall well tolerated. Vaccine-induced immune responses were seen in the majority of patients in the adjuvant setting and in the presence of advanced disease."

Clinical • P1/2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • CD4 • IFNG

BioNTech to Present Clinical Data Updates Across mRNA and Immunomodulatory Oncology Portfolio at ESMO Congress 2024 (GlobeNewswire) - "Preliminary data from an ongoing clinical Phase 2 trial (NCT04534205) evaluating BNT113 in combination with PD-1 blockade and data from an investigator-initiated Phase 1/2 clinical trial (NCT03418480) evaluating BNT113 as monotherapy in HPV16-driven cancers will be presented. The data show immunogenicity and antitumor activity in heavily pre-treated patients in several HPV16-positive indications, including head and neck cancer, and a manageable safety profile. BNT113 is an investigational lipoplex-formulated uridine mRNA immunotherapy encoding E6 and E7 antigens of HPV16."

P1/2 data • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

BioNTech Announces Second Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "A global, randomized Phase 2 clinical trial (NCT04534205) evaluating BNT113 in combination with pembrolizumab versus pembrolizumab monotherapy as a first-line treatment in patients with unresectable recurrent or metastatic HPV16+ head and neck squamous cell carcinoma expressing PD-L1 is ongoing. Data updates are expected to be presented at the 2024 Congress of the European Society of Medical Oncology ('ESMO') taking place from September 13-17, 2024 in Barcelona, Spain....Preliminary data from the ongoing Phase 2 clinical trial (NCT04486378) in stage II (high risk) and III ctDNA+ adjuvant CRC is expected in late 2025 or 2026."

P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

HARE-40: HPV Anti-CD40 RNA vaccinE (clinicaltrials.gov) - P1/2 | N=32 | Completed | Sponsor: University of Southampton | Active, not recruiting ➔ Completed

Trial completion • Cervical Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

AHEAD-MERIT: A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 (clinicaltrials.gov) - P2 | N=285 | Recruiting | Sponsor: BioNTech SE

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

HARE-40: HPV Anti-CD40 RNA vaccinE (clinicaltrials.gov) - P1/2 | N=32 | Active, not recruiting | Sponsor: University of Southampton | Suspended ➔ Active, not recruiting

Enrollment closed • Cervical Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

HARE-40: HPV Anti-CD40 RNA vaccinE (clinicaltrials.gov) - P1/2 | N=44 | Suspended | Sponsor: University of Southampton | Trial completion date: Oct 2024 ➔ Apr 2025 | Recruiting ➔ Suspended | Trial primary completion date: Jul 2024 ➔ Oct 2023

Trial completion date • Trial primary completion date • Trial suspension • Cervical Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

BNT113 + pembrolizumab as first-line treatment in patients with unresectable recurrent/metastatic HNSCC: Preliminary safety data from AHEAD-MERIT (ESMO-IO 2022) - P2 | "Conclusions Safety was acceptable and in line with the safety profile of BNT113 and pembrolizumab as single agents; no new safety signals were observed for the combination. The randomized part of the trial is ongoing."

Clinical • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

BioNTech plans clinical trial hub for mRNA-based cancer immunotherapies in Taiwan as part of Asia Pacific expansion [Google Translation] (BioNTech Press Release) - "BioNTech SE...announced plans to expand its clinical footprint into East Asia to accelerate and expand the development of its proprietary cancer immunotherapy pipeline in the Asia-Pacific region. BioNTech intends to activate the first clinical study centers for mRNA-based cancer immunotherapies in this region in Taiwan. The first product candidate is said to be BNT113, an mRNA therapy against head and neck cancer. BNT113 is expected to be the first product candidate in a potential wave of novel cancer immunotherapies that BioNTech intends to evaluate in the region. These plans are part of BioNTech's Asia Pacific strategy aimed at developing, manufacturing and expanding access to innovative medicines. The focus is on therapies for the types of cancer that occur most frequently in Asia. As part of these plans, BioNTech is collaborating with the YongLin Healthcare Foundation and signed a Memorandum of Understanding with Retain Biotech Corp. in November 2022."

Pipeline update • Head and Neck Cancer • Oncology

AHEAD-MERIT: A Clinical Trial Investigating the Safety, Tolerability, and Therapeutic Effects of BNT113 in Combination With Pembrolizumab Versus Pembrolizumab Alone for Patients With a Form of Head and Neck Cancer Positive for Human Papilloma Virus 16 and Expressing the Protein PD-L1 (clinicaltrials.gov) - P2 | N=285 | Recruiting | Sponsor: BioNTech SE | Trial completion date: May 2025 ➔ May 2028 | Trial primary completion date: May 2025 ➔ May 2028

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

HARE-40: HPV Anti-CD40 RNA Vaccine (clinicaltrials.gov) - P1/2 | N=44 | Recruiting | Sponsor: University of Southampton | Active, not recruiting ➔ Recruiting | Trial completion date: Dec 2023 ➔ Oct 2024 | Trial primary completion date: Mar 2023 ➔ Jul 2024

Enrollment open • Trial completion date • Trial primary completion date • Cervical Cancer • Genito-urinary Cancer • Head and Neck Cancer • Oncology • Penile Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

BioNTech Announces First Patient Dosed in Phase 2 Clinical Trial of mRNA-based BNT111 in Patients with Advanced Melanoma (GlobeNewswire) - “BioNTech…announced today that the first patient has been treated in its BNT111 Phase 2 cancer vaccine trial…The study is evaluating the Company’s therapeutic cancer vaccine candidate BNT111 in combination with Libtayo® (cemiplimab) in patients with anti-PD1-refractory/relapsed unresectable Stage III or IV melanoma. BNT111 is the lead product candidate from BioNTech’s FixVac platform that targets a fixed combination of mRNA-encoded, tumor-associated antigens with the objective of triggering a strong and precise immune response against cancer and is fully owned by BioNTech…The Company also plans to start randomized Phase 2 trials with mRNA vaccine product candidates in two additional programs in 2021 (FixVac: BNT113 and iNeST: BNT122).”

Trial status • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer