BNT111 / BioNTech - LARVOL DELTA

In October, data from a randomized Phase 2 clinical trial (BNT111-01; NCT04526899) conducted in collaboration with Regeneron Pharmaceuticals Inc. ("Regeneron”) to evaluate BNT111 in combination with cemiplimab in patients with anti-PD-(L)1 refractory/relapsed, unresectable Stage III or IV melanoma were presented at the 2025 ESMO Congress. (The Manila Times) - "As previously disclosed, the trial met its primary endpoint demonstrating statistically significant improvement in objective response rate ('ORR') in patients treated with BNT111 in combination with cemiplimab, as compared to an historical control. The data showed that the combination of BNT111 and cemiplimab induced anti-tumor responses that were deep and durable and a manageable safety profile for BNT111 as a single agent and in combination."

P2 data • Melanoma

Primary results from a randomized phase II trial of BNT111 in combination with cemiplimab with calibrator monotherapy arms in anti-PD-(L)1 relapsed/refractory melanoma (ESMO 2025) - P2 | "BNT111 also indicated clinical activity as monotherapy. No meaningful differences in median PFS or OS were noted between combination and monotherapies."

Clinical • Combination therapy • IO biomarker • Monotherapy • P2 data • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • CTAG1B • Tyrosinase

BioNTech fades out further work with cancer vaccine prospect in late-stage melanoma setting (FierceBiotech) - "BioNTech won’t proceed with further development of its BNT111 cancer vaccine candidate in a specific late-stage refractory melanoma setting, a company spokesperson told Fierce Biotech. The decision to push pause is 'in line with our strategy' as BioNTech focuses on other programs from its FixVac mRNA platform....BioNTech presented results....At a median follow-up of 15.7 months, the median amount of time that patients in the study's BNT111-Libtayo arm survived without their disease getting worse came to 3.1 months. The regimen was associated with a 24-month progression-free survival rate of 24.9%, as well....As for overall survival, patients who received the Libtayo-vaccine combo lived a median of 20.7 months, according to the presentation. After 24 months of follow-up, the combination regimen was associated with a survival rate of 47.8%."

Discontinued • P2 data • Melanoma

Shared epitopes create safety and efficacy concerns in several cancer vaccines. (PubMed, J Immunother Cancer) - "Altogether, our analysis indicates a suboptimal design of several cancer vaccines currently in clinical development: ATP128, BNT111, BNT112, BNT116, INO-5401. We recommend that next-generation cancer vaccines should integrate rigorous epitope filtering strategies to eliminate shared sequences in TAAs."

Journal • Immunology • Oncology • ASCL2 • CLDN6 • KLK2

BNT111-01: A Study to Investigate the Novel Agent BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Advanced Melanoma That Has Not Responded to Other Forms of Treatment (clinicaltrials.gov) - P2 | N=184 | Active, not recruiting | Sponsor: BioNTech SE | Trial completion date: Jul 2026 ➔ Dec 2025

Trial completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

BioNTech Announces Fourth Quarter and Full Year 2024 Financial Results and Corporate Update (GlobeNewswire) - "First data from the ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran as an adjuvant treatment compared to watchful waiting after standard of care chemotherapy in resected circulating tumor DNA+ ('ctDNA') stage II (high-risk) and III colorectal cancer ('CRC') are anticipated in late 2025 or early 2026. BNT111 is based on BioNTech’s fully owned, off-the-shelf FixVac platform, and encodes four melanoma-associated antigens. BioNTech plans to present data from the ongoing Phase 2 clinical trial (BNT111-01; NCT04526899) at a medical conference in 2025."

P2 data • Colorectal Cancer • Melanoma

BioNTech Announces Third Quarter 2024 Financial Results and Corporate Update (BioNTech Press Release) - "BNT327/PM8002...A Phase 2/3 clinical trial in first-line non-small cell lung cancer ('NSCLC') is expected to start in 2024...Data in first-line TNBC are planned to be presented at the San Antonio Breast Cancer Symposium, taking place from December 10 to December 13 in San Antonio, Texas, U.S. Additional data are expected to be presented in 2025...A randomized Phase 2 clinical trial (BNT111-01; NCT04526899) is being conducted...to evaluate BNT111 in combination with cemiplimab in patients with anti-PD-(L)1 refractory/relapsed, unresectable stage III or IV melanoma...BioNTech plans to present data from this trial at an upcoming medical conference in 2025...BNT324...A first-in-human, open-label Phase 1/2 clinical trial (NCT05914116) in patients with advanced solid tumors is ongoing....The first preliminary data update from this trial is expected to be presented at the ESMO Asia Congress (December 6-8, 2024 in Singapore)."

Clinical data • New P2/3 trial • Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Triple Negative Breast Cancer

Partial remission of an advanced, therapy-refractory melanoma under therapy with tumor-infiltrating lymphocytes (TIL) (ADO 2024) - "Introduction: In February 2024, therapy with tumor-infiltrating lymphocytes (TIL) received FDA approval under the name Lifileucel as the first commercial procedure for solid tumors with an overall response rate of 34% for therapy-refractory metastatic melanoma patients1...After progression in the BNT 111 protocol (cemiplimab plus mRNA vaccine BNT 111), radiosurgery and immune combination therapy followed in October 2022...During maintenance therapy with nivolumab, new hepatic, renal and cervical metastases occurred...After additional treatment of individual progressive soft tissue metastases by excision and intralesional T-VEC, no metastases were detectable in the PET-CT in February 2024...Even if TIL therapy did not achieve a primary complete remission, it laid the foundation for comprehensive tumor control in a heavily pretreated patient. However, due to the complexity and the almost obligatory, more severe side effects, which are mostly related to the cytoreductive..."

Clinical • Metastases • Tumor-infiltrating lymphocyte • Gastroenterology • Gastrointestinal Disorder • Immunology • Melanoma • Oncology • Solid Tumor • BRAF

mRNA vaccines: a new era in vaccine development. (PubMed, Oncol Res) - "Pioneering candidates, such as BioNTech's BNT111 and Moderna's mRNA-4157, have exhibited promising outcomes in targeting melanoma and solid tumors, respectively. Overall, mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment. As research progresses, addressing challenges and refining manufacturing processes will be crucial in advancing these vaccines from clinical trials to mainstream oncology practice, offering new hope for patients in the fight against cancer."

Journal • Review • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor

BNT111-01: Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma (clinicaltrials.gov) - P2 | N=184 | Active, not recruiting | Sponsor: BioNTech SE | Trial primary completion date: Nov 2025 ➔ Jan 2024

Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Buy Rating for Evaxion Biotech: EVX-01’s Personalized Cancer Vaccine Shows Promising Efficacy and Safety (Markets Insider) - "Analyst Swayampakula Ramakanth of H.C. Wainwright reiterated a Buy rating on Evaxion Biotech...retaining the price target of $14.00....Swayampakula Ramakanth’s rating is based on the unique positioning and promising clinical data of Evaxion Biotech’s EVX-01 as a personalized cancer vaccine. Ramakanth highlights the distinction between EVX-01 and other therapies, such as BNT111, noting that EVX-01 targets a personalized set of neoantigens specific to each patient’s cancer, potentially leading to a wider range of efficacy and safety. He posits that EVX-01’s design to address individual tumor characteristics could offer superior efficacy and reduced toxicity compared to less personalized approaches."

Stock price • Melanoma • Oncology • Skin Cancer • Solid Tumor

BioNTech Announces Positive Topline Phase 2 Results for mRNA Immunotherapy Candidate BNT111 in Patients with Advanced Melanoma (GlobeNewswire) - P2 | N=184 | NCT04526899 | Sponsor: BioNTech SE | "BioNTech SE...announced positive topline data from the ongoing Phase 2 clinical trial (EudraCT No.: 2020-002195-12; NCT04526899) in patients with unresectable stage III or IV melanoma whose disease had progressed following anti-PD-(L)1-containing treatment....The trial met its primary efficacy outcome measure, demonstrating a statistically significant improvement in ORR in patients treated with BNT111 in combination with cemiplimab as compared to historical control in this indication and treatment setting. Both randomized monotherapy arms showed clinical activity. The ORR in the cemiplimab monotherapy arm was in line with the historical control of anti-PD-(L)1 or anti-CTLA-4 treatments in this patient group....BioNTech and Regeneron plan to present data from this trial at a forthcoming medical conference."

P2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Expression of the tumor antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in pediatric and adult melanoma: a retrospective case control study. (PubMed, Virchows Arch) - "BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma."

IO biomarker • Journal • Retrospective data • Cutaneous Melanoma • Melanoma • Oncology • Pediatrics • Solid Tumor • CTAG1B • Tyrosinase

Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma (clinicaltrials.gov) - P2 | N=184 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

Enrollment closed • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Jun 2025 ➔ Jul 2026 | Trial primary completion date: Oct 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Lipo-MERIT: Evaluation of the Safety and Tolerability of i.v. Administration of a Cancer Vaccine in Patients With Advanced Melanoma (clinicaltrials.gov) - P1 | N=119 | Completed | Sponsor: BioNTech SE | Active, not recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor • CTAG1B

A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for immunotherapy of malignant melanoma (ESMO 2018) - P1; "...We have developed a novel class of RNA-lipoplex (RNA(LIP)) immunotherapeutics for intravenous application allowing systemic targeting of antigen-presenting cells (APCs)...Pharmacodynamic activity and immunogenicity of the vaccine is investigated by concerted immune monitoring and correlative biomarker studies. Clinical activity is assessed following imaging according to irRECIST1.1."

Clinical • IO biomarker • P1/2 data • Melanoma

BioNTech Strengthens Manufacturing Capabilities with First In-House Plasmid DNA Manufacturing Facility (GlobeNewswire) - "BioNTech SE...announced construction completion of the Company’s first proprietary plasmid DNA manufacturing facility in Marburg, Germany....BioNTech plans to independently manufacture the majority of its own current regular demand for DNA plasmids in the new manufacturing facility, once it is operational and pending regulatory approvals....In this plant, BioNTech is currently manufacturing plasmids for the Company’s FixVac platform product candidates, such as BNT111. BioNTech expects to manufacture plasmid DNA that can be utilized as starting material to manufacture mRNA for several hundred million vaccine doses or therapies annually, depending on the product or product candidate. The commercial plant is anticipated to be operational by the end of 2023, subject to regulatory approval. BioNTech expects a total investment of around €40 million in the new manufacturing facility."

Commercial • Oncology

An RNA-lipoplex (RNA-LPX) vaccine demonstrates strong immunogenicity and promising clinical activity in a Phase I trial in cutaneous melanoma patients with no evidence of disease at trial inclusion (SITC 2021) - P1 | "Background Lipo-MERIT is an ongoing, first-in-human, open-label, dose-escalation Phase I trial investigating safety, tolerability and immunogenicity of BNT111 in patients with advanced melanoma...Trial Registration Clinicaltrials.gov: NCT02410733; EudraCT No. 2013-001646-33."

Clinical • P1 data • Cutaneous Melanoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Melanoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4 • CTAG1B • IFNG • MAGEA3 • Tyrosinase

The paradigm shift in treatment from Covid-19 to oncology with mRNA vaccines. (PubMed, Cancer Treat Rev) - "The rapid development and large-scale production of mRNA platform has enabled for the development of both personalized vaccines (mRNA 4157, mRNA 4650 and RO7198457) and tetravalent vaccines (BNT111 and mRNA-5671). In other words, while developing a vaccine design, the underlying motivation should be a reasonable combination of delivery route and format. Exploring various administration routes and delivery route systems has boosted the development of mRNA vaccines."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. (PubMed, Nature) - P1 | "We are testing melanoma FixVac (BNT111)-an intravenously administered liposomal RNA (RNA-LPX) vaccine, which targets four non-mutated, tumour-associated antigens that are prevalent in melanoma-in an ongoing, first-in-human, dose-escalation phase I trial in patients with advanced melanoma (Lipo-MERIT trial, ClinicalTrials.gov identifier NCT02410733)...The antigen-specific cytotoxic T-cell responses in some responders reach magnitudes typically reported for adoptive T-cell therapy, and are durable. Our findings indicate that RNA-LPX vaccination is a potent immunotherapy in patients with CPI-experienced melanoma, and suggest the general utility of non-mutant shared tumour antigens as targets for cancer vaccination."

Checkpoint inhibition • IO Biomarker • Journal • Melanoma • Oncology • Solid Tumor

Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Dec 2023 ➔ Jun 2025 | Trial primary completion date: May 2022 ➔ Oct 2024

Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

Ongoing Research Into Cancer Vaccine Candidate BNT111 at Atlantic Health System (Cancer Network) - '"The ideal candidate for this trial is someone with advanced melanoma who has failed to respond to standard therapy,' Whitman said. 'They've run out of FDA-approved options. One of the important things for this trial is that they can't have had such severe adverse effects with FDA-approved immunotherapies.'"

Interview

Trial With BNT111 and Cemiplimab in Combination or as Single Agents in Patients With Anti-PD-1-refractory/Relapsed, Unresectable Stage III or IV Melanoma (clinicaltrials.gov) - P2; N=180; Recruiting; Sponsor: BioNTech SE; N=120 ➔ 180

Clinical • Enrollment change • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF

BioNTech Receives FDA Fast Track Designation for its FixVac Candidate BNT111 in Advanced Melanoma (GlobeNewswire) - "BioNTech SE...announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for BNT111, an investigational cancer immunotherapy for the potential treatment of advanced melanoma. BNT111 is the lead product candidate from BioNTech’s fully owned FixVac platform that utilizes a fixed combination of mRNA-encoded, tumor-associated antigens aiming to trigger a strong and precise immune response against cancer."

Fast track designation • Melanoma • Oncology