BNT113 / BioNTech - LARVOL DELTA

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

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; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

BioNTech Announces Full Year 2020 Financial Results and Corporate Update (GlobeNewswire) - “BNT111 – We expect to start a randomized Phase 2 trial for the treatment of patients with advanced melanoma progressing during or after prior therapy with a PD-1 inhibitor, utilizing a combination of BNT111 and Regeneron and Sanofi’s Libtayo® (Cemiplimab) in the first half of 2021 in the United States and the European Union…BNT113 – We expect to start a Phase 2 trial 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 (HNSCC) expressing PD-L1 in the first half of 2021 in the United States and the European Union.”

New P2 trial • Cutaneous Melanoma • Head and Neck Cancer • Melanoma • Oncology • Skin Cancer • Squamous Cell Carcinoma of Head and Neck

HARE-40: HPV Anti-CD40 RNA Vaccine (clinicaltrials.gov) - P1/2; N=44; 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 • Squamous Cell Carcinoma of Head and Neck

BioNTech Announces Third Quarter 2020 Financial Results and Corporate Progress (GlobeNewswire) - "In July, BioNTech and Regeneron announced a strategic collaboration to jointly conduct a randomized Phase 2 trial for the treatment of patients with melanoma progressing during or after prior therapy with a PD-1 inhibitor, utilizing a combination of BNT111 and Regeneron’s Libtayo^®. This trial is currently under review by the FDA. We are currently targeting commencement of the trial in the first half of 2021, subject to allowance of the IND by the FDA; BNT113 – Planned initiation of a randomized Phase 2 trial in HPV16+ head and neck cancer is currently under review by the FDA. We are currently targeting commencement of the trial in the first half of 2021..."

IND • New P2 trial • Head and Neck Cancer • Melanoma • Oncology

QIAGEN Collaborates with BioNTech on Companion Diagnostics Development for HPV-associated Squamous Cell Carcinoma of the Head and Neck (Businesswire) - "QIAGEN...announced a strategic collaboration with BioNTech...to develop and commercialize a tissue-based companion diagnostic – to be used with investigational cancer treatment BNT113 – which identifies patients with squamous cell carcinoma of the head and neck (SCCHN) that are caused by specific infections by human papilloma virus (HPV)...QIAGEN plans to expand the panel for use across HPV-driven cancers such as cervical cancer and other cancers, in order to provide a universal HPV companion diagnostic (CDx) for QIAGEN’s pharmaceutical partners."

Diagnostic • Licensing / partnership • Cervical Cancer • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck

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; Not yet recruiting; Sponsor: BioNTech SE

Clinical • Combination therapy • Monotherapy • New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

BioNTech Announces Second Quarter 2020 Financial Results and Corporate Progress (GlobeNewswire) - "BNT111 – BioNTech expects to initiate this Phase 2 trial with registrational potential in the second half of 2020. BNT113 – Planned initiation of a potentially registrational Phase 2 trial in HPV16+ head and neck cancer expected in 2H 2020. BNT114 – Planned data update from a Phase 1 trial in triple negative breast cancer (TNBC) is expected in 2H 2020....BNT122 – BioNTech expects to provide an enrollment update from the Phase 2 trial (IMCODE-001) in first line melanoma in 2H 2020 with an interim data update anticipated in 2H 2021. BNT122 –The first adjuvant Phase 2 study is currently recruiting for patients and first patient dosing is expected in 2H 2020. The trial is designed to evaluate the efficacy and safety of RO7198457 (BNT122/RG6180) plus atezolizumab compared with atezolizumab alone in patients with early and adjuvant stage non-small-cell lung cancer (NSCLC). The second Phase 2 study will be in colorectal cancer in adjuvant setting and is expected to initiate in 2H 2020."

Enrollment status • New P2 trial • P1 data • Breast Cancer • Melanoma • Oncology • Triple Negative Breast Cancer

BioNTech announces first quarter 2020 financial results and corporate progress (GlobeNewswire) - "There are currently ten oncology products in 11 ongoing trials with multiple data readouts expected in 2020....BNT111 – Data from a Phase 1 trial in advanced melanoma remains on track for publication in late 1H 2020. BioNTech expects to initiate a Phase 2 trial in advanced melanoma with registrational potential for BNT111 in 2H 2020; BNT 113 – Initiation of a Phase 2 trial in HPV+ head and neck cancer with registrational potential is on track for 2H 2020; BNT114 – Data update from a Phase 1 trial in triple negative breast cancer (TNBC) is expected in 2H 2020."

Clinical data • New P2 trial • P1 data • Breast Cancer • Head and Neck Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

HARE-40: HPV Anti-CD40 RNA Vaccine (clinicaltrials.gov) - P1/2; N=44; Suspended; Sponsor: University of Southampton; Trial completion date: Dec 2020 ➔ Dec 2023; Recruiting ➔ Suspended; Trial primary completion date: Sep 2019 ➔ Mar 2023

Trial completion date • Trial primary completion date • Trial suspension