BNT211 / BioNTech - LARVOL DELTA

Updated results from BNT211-01 (NCT04503278), an ongoing, first-in-human, phase I study evaluating safety and efficacy of CLDN6 CAR T cells and a CLDN6-encoding mRNA vaccine in patients with relapsed/refractory CLDN6+ solid tumors (ESMO 2024) - P1 | "CLDN6 CAR T cells ± CARVac showed treatment-related safety signals and promising antitumor activity in pts with r/r CLDN6+ solid tumors."

CAR T-Cell Therapy • Clinical • P1 data • Oncology • Solid Tumor • CLDN6

BioNTech to Present Clinical Data Updates Across mRNA and Immunomodulatory Oncology Portfolio at ESMO Congress 2024 (GlobeNewswire) - "Follow-up data of activity and immune responses from the ongoing first-in-human Phase 1 clinical trial (NCT04503278) with BNT211 in patients with relapsed/refractory CLDN6+ solid tumors will be presented. BNT211 combines autologous CAR-T cells directed against the oncofetal antigen Claudin-6 ('CLDN6') and an CLDN6-encoding CAR-T cell amplifying mRNA vaccine ('CARVac'). The data update shows signs of antitumor activity across all indications and an increased persistence of cancer-specific CAR-T cells when combined with CARVac, for example in patients with testicular and ovarian cancers. The safety profile is consistent with the previously published data of CAR-T therapies."

P1 data • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer

BioNTech Announces Second Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "In July 2024, the U.S. FDA granted Orphan Drug designation to BNT324/DB-1311 for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma....A first-in-human, open-label, multi-center Phase 1 dose escalation and dose expansion basket trial (NCT04503278) evaluating CLDN6 CAR-T cells as monotherapy or in combination with CLDN6 CARVac in patients with CLDN6-positive relapsed or refractory solid tumors, including ovarian cancers and testicular germ cell tumors, is ongoing. A data update is expected to be presented at the 2024 ESMO Congress."

Orphan drug • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer

Fetal gut cell-like differentiation in esophageal adenocarcinoma defines a rare tumor subtype with therapeutically relevant claudin-6 positivity and SWI/SNF gene alteration. (PubMed, Sci Rep) - P1 | "Furthermore, claudin-6 positive tumors have shown promising efficacy of CAR T cell therapy in the recently published BNT-211-01 trial (NCT04503278). This represents a personalized therapeutic option for this tumor subtype."

Biomarker • Journal • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CLDN6 • GPC3 • SALL4

BioNTech Announces First Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "Autogene cevumeran (BNT122) is a uridine mRNA-lipoplex based cancer vaccine candidate for individualized neoantigen-specific immunotherapy ('iNeST') being developed in collaboration with Genentech, Inc., a member of the Roche Group ('Genentech')....Epidemiologic data including post-operative circulating tumor DNA ('ctDNA') prevalence and prognostic value from a non-interventional, observational study (NCT04813627) in patients with resected high-risk stage II/III CRC are expected to be presented at the 2024 ASCO Annual Meeting. A Phase 2 clinical trial in an additional indication is planned. BNT211 consists of two investigational medicinal products...BioNTech plans to present an analysis of real world evidence investigating overall survival and treatment patterns of patients with testicular germ cell tumors receiving palliative chemotherapy at the 2024 ASCO Annual Meeting."

Observational data • Real-world evidence • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Testicular Cancer

Car -T therapy: a promising immunotherapeutic approach to testicle cancer - an updated review (ICUC 2024) - "Therefore, it is concluded that focus therapy is promising, given the effectiveness in preclinical and clinical tests.However, few studies have been carried out and the samples are small, requiring further research to evaluate the degree of efficacy of such conduct."

IO biomarker • Review • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor • Testicular Cancer • CLDN6 • TNFRSF8

CARVac: A Clinical Study of the Safety and Effectiveness of an Investigational Cell Therapy Given With and Without an Investigational RNA-based Vaccine in Patients With Organ Tumors (clinicaltrials.gov) - P1 | N=145 | Recruiting | Sponsor: BioNTech Cell & Gene Therapies GmbH | Phase classification: P1/2 ➔ P1 | Trial completion date: Sep 2037 ➔ Jan 2040 | Trial primary completion date: Aug 2024 ➔ Jan 2027

Metastases • Phase classification • Trial completion date • Trial primary completion date • Germ Cell Tumors • Oncology • Solid Tumor • AFP • CLDN6

BioNTech and Autolus Announce Strategic CAR-T Cell Therapy Collaboration to Advance Pipeline and Expand Late-Stage Programs (GlobeNewswire) - "BioNTech SE...and Autolus Therapeutics plc...today announced a strategic collaboration aimed at advancing both companies’ autologous CAR-T programs towards commercialization, pending regulatory authorizations...Under the terms of the license and option agreement, BioNTech will make a cash payment of $50 million and is granted the following rights in exchange: BioNTech is eligible to receive an up to mid-single digit royalty on obe-cel net sales. Autolus will retain full rights to and control of the development and commercialization of obe-cel; BioNTech has the option to access Autolus’ commercial and clinical site network, manufacturing capacities in the United Kingdom and commercial supply infrastructure in a cost-efficient set-up in order to accelerate the development of BNT211 in additional CLDN6+ tumor types. BioNTech plans to have 10 or more ongoing potentially registrational clinical trials in the pipeline by the end of 2024..."

Licensing / partnership • New trial • Acute Lymphocytic Leukemia • CNS Lymphoma • Genito-urinary Cancer • Germ Cell Tumors • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond (ScienceDirect) - "The clinical trial evaluating the combination of mRNA-4157 and anti-programmed cell death protein 1 (PD-1) has demonstrated remarkable success in reducing the distant metastases and death by 65 % compared to treatment with PD-1 alone...Another successful approach involving LNPs are CAR antigen vaccines (CARVac)...In a clinical trial conducted by BioNTech, a combination of CAR-T therapy targeting the CLDN6 antigen and an mRNA vaccine (CARVac) encoding for the CLDN6 antigen was utilized for the treatment of solid tumors. The findings of the study revealed that the mRNA vaccine significantly enhanced the antitumor efficacy of CAR-T cells. Additionally, the combined treatment demonstrated a favourable safety profile..."

Clinical data • Lipid Nanoparticle • Oncology

BioNTech Outlines 2024 Strategic Priorities at the 42nd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "BNT122 (autogene cevumeran) is an mRNA cancer vaccine candidate based on an individualized neoantigen-specific immunotherapy (iNeST) approach being developed in collaboration with Genentech Inc. (“Genentech”), a member of the Roche Group....An additional Phase 2 trial is planned to be initiated as early as late 2024. BNT211 consists of two investigational medicinal products: a CAR-T cell product candidate targeting Claudin-6 (CLDN6)-positive solid tumors, in combination with a CAR-T cell-amplifying RNA vaccine (CARVac) encoding CLDN6. BioNTech plans to initiate a pivotal Phase 2 trial in relapsed/refractory germ cell tumors in 2024."

New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Germ Cell Tumors • Oncology • Solid Tumor

CARVac: A Trial to Evaluate the Safety and Efficacy of CLDN6 CAR-T +/- CLDN6 RNA-LPX (clinicaltrials.gov) - P1/2 | N=114 | Recruiting | Sponsor: BioNTech Cell & Gene Therapies GmbH

Metastases • Trial completion date • Trial primary completion date • Germ Cell Tumors • Oncology • Solid Tumor • AFP • CLDN6

CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors: the phase 1 BNT211-01 trial. (PubMed, Nat Med) - P1/2 | "A repeat of the dose escalation is ongoing and will identify a RP2D for pivotal trials. ClinicalTrials.gov Identifier: NCT04503278 ."

CAR T-Cell Therapy • Journal • P1 data • Germ Cell Tumors • Oncology • Solid Tumor • CLDN6

BNT211-01: Interim results from a repeat dose escalation study of CLDN6 CAR-T cells manufactured with an automated process ± a CLDN6-encoding CAR-T cell-amplifying RNA Vaccine (CARVac) (ESMO 2023) - P1/2 | "The safety profile in terms of CRS, ICANS and DLTs observed is in line with previously reported observations. We intend to present data on up to 42 pts, with a data cut-off of 10.09.2023."

CAR T-Cell Therapy • Late-breaking abstract • Germ Cell Tumors • Oncology • Ovarian Cancer • Solid Tumor • CLDN6

BioNTech Presents Positive Phase 1/2 Data Update for CAR-T Cell Therapy Candidate BNT211 in Advanced Solid Tumors at ESMO Congress 2023 (GlobeNewswire) - P1/2 | N=114 | NCT04503278 | Sponsor: BioNTech Cell & Gene Therapies GmbH | "In course of the dose escalation, a dose-dependent increase in adverse events was observed, with cytokine release syndromes occurring in 23 of 44 safety evaluable patients. In most cases, these were of grade 1 and 2, with one patient with a grade 3 and one with a grade 4 event. Neurotoxicity was mild and self-limiting in two patients. Of the total 44 patients, 38 were efficacy evaluable. The overall response rate ('ORR') for these 38 patients was 45% and the disease control rate ('DCR') 74%....One objective of the ongoing Phase 1/2 trial is to determine the recommended dose for the initiation of a potential pivotal Phase 2 trial in patients with germ cell tumors which is expected to be initiated in 2024."

P1 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

BioNTech to Present Multiple Program Updates Across Modalities at ESMO Congress 2023 (GlobeNewswire) - "BioNTech SE...will present data across its oncology pipeline, covering multiple solid tumor types and novel mechanisms of action, at the European Society for Molecular Oncology ('ESMO') Congress 2023 in Madrid, Spain from October 20-24, 2023....BioNTech will present new data of its investigational autologous Claudin-6 (CLDN6)-directed CAR-T cell therapy BNT211 (NCT04503278), including data showing the potential of combining these CAR-T cells with a CLDN6-encoding CAR-T cell amplifying mRNA vaccine ('CARVac'). Initial data from BioNTech's first-in-human Phase 1 study with BNT221 (NCT04625205), a personalized, autologous neoantigen-specific T cell therapy, will be presented. The initial results show a manageable safety profile and tumor regression in several patients with anti-PD-1 and anti-CTLA4 pretreated advanced or metastatic melanoma."

P1 data • P1/2 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

BNT211-01: A Trial to Evaluate the Safety and Efficacy of CLDN6 CAR-T +/- CLDN6 RNA-LPX (clinicaltrials.gov) - P1/2 | N=114 | Recruiting | Sponsor: BioNTech Cell & Gene Therapies GmbH | Trial completion date: Sep 2036 ➔ Sep 2037 | Trial primary completion date: Aug 2023 ➔ Aug 2024

Metastases • Trial completion date • Trial primary completion date • Germ Cell Tumors • Oncology • Solid Tumor • AFP • CLDN6 • IL2

BioNTech Announces Second Quarter 2023 Financial Results and Corporate Update (GlobeNewswire) - "BNT324/DB-1311 is a topoisomerase-1 inhibitor-based ADC candidate being developed in collaboration with DualityBio. A first-in-human, open-label Phase 1/2 clinical trial evaluating BNT324/DB-1311 in multiple advanced solid tumors is planned to start this year....BNT211 is an autologous Claudin-6 (CLDN6)-targeting chimeric antigen receptor (CAR) T cell therapy candidate that is being tested alone and in combination with an investigational CAR-T cell Amplifying RNA Vaccine compound, or CARVac, encoding CLDN6....After determination of a recommended Phase 2 dose for CLDN6 CAR-T cells, a pivotal trial in germ cell tumors is planned to start in 2024."

New P1/2 trial • New trial • Oncology • Solid Tumor

CLDN6 CAR-T cell therapy of relapsed/refractory solid tumors ± a CLDN6-encoding mRNA vaccine: Dose escalation data from the BNT211-01 phase 1 trial using an automated product. (ASCO 2023) - P1/2 | "We intend to submit efficacy, safety and CAR T-cell pharmacokinetics data from 5 cohorts treated with 1x106, 1x107 or 1x108 CLDN6 CAR-T cells ± CARVac with a data cut-off of March 14th, 2023 from ≥17 treated patients as a late-breaking abstract. Clinical trial information: NCT04503278."

CAR T-Cell Therapy • IO biomarker • P1 data • Germ Cell Tumors • Hematological Malignancies • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6

Efficacy of CLDN6-Directed CAR T Therapy Is Maintained With Automated Manufacturing in Solid Tumors (OncLive) - P1/2a | N=96 | NCT04503278 | Sponsor: BioNTech Cell & Gene Therapies GmbH | "When manufactured via automated process the CLDN6-directed CAR T-cell therapy, BNT211, demonstrated encouraging signs of activity and a manageable safety profile with or without the addition of CLDN6-encoding mRNA vaccine (CARVac) in patients with CLDN6-positive relapsed/refractory advanced solid tumors, according to findings from the phase 1/2a trial (NCT04503278).... The disease-control rate (DCR) was 65%....Efficacy was deemed comparable by investigators to the manual product analysis, which elicited an ORR of 33%, including 1 patient with a complete response (CR) and 6 patients with a PR. Seven patients reported stable disease (SD) and the DCR was 67%.2 Investigators also presented an update from the manual product cohort, which showed that 3 of the 13 patients with germ cell tumors had ongoing clinical benefit as of the March 10, 2023, data cutoff."

P1/2 data • Oncology • Solid Tumor

ASCO 2023 Spotlight: Claudin 6 Anticipated To Shine (Issuer Direct) - "At ASCO 2023, BioNTech and TORL will present Phase 1 clinical trial data on CLDN6-targeted programs, including BNT142, BNT211, and TORL-1-23....BioNTech will present multiple updates from its CLDN portfolio, most notably an update from their CLDN-6-targeting CAR-T cell therapy, BNT211, in combination with CLDN6- encoding mRNA vaccine (CARVac) in solid tumors (poster #2518)....BioNTech will also provide a trial-in-progress update for BNT142 (mRNA vaccine encoding a CD3 x CLDN-6 bispecific, poster abstract TPS2669)....TORL Biotherapeutics will present the first clinical data from its CLDN6 ADC TORL-1-23."

P1 data • Trial status • Oncology • Solid Tumor

BNT211: A Phase I trial to evaluate safety and efficacy of CLDN6 CAR-T cells and CARVac-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumors (AACR 2022) - P1/2 | "CLDN6 CAR-T cells ± CARVac show an acceptable safety profile at doses tested and encouraging signs of clinical activity. Data from the completed dose escalation phase will be presented. Acknowledgements: BNT211-01 is funded by BioNTech Cell & Gene Therapies GmbH.Trial registration: Clinicaltrials.gov: NCT04503278.Ethics approval: Ethics & Institutional Review Board approvals were obtained from the respective participating countries prior to initiation of the trial."

CAR T-Cell Therapy • P1 data • Preclinical • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6

BNT211-01: A phase I trial to evaluate safety and efficacy of CLDN6 CAR T cells and CLDN6-encoding mRNA vaccine-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumours (ESMO 2022) - P1/2 | "5 pts with testicular cancer responded at 6 wks, with CAR T-cell persistence and further tumour shrinkage; 1 pt was investigator-assessed as CR after 18 wks (negative PET-CT and tumour-marker negative). Conclusions CLDN6 CAR T cells ± CLDN6 CARVac had a manageable safety profile in this first-in-human trial, with encouraging signs of clinical activity in pts with limited treatment options."

CAR T-Cell Therapy • Late-breaking abstract • P1 data • Preclinical • Genito-urinary Cancer • Oncology • Ovarian Cancer • Solid Tumor • Testicular Cancer • CLDN6

BioNTech Announces Fourth Quarter and Full Year 2022 Financial Results and Corporate Update (GlobeNewswire) - "In 2023, BioNTech and Genentech are expecting a data update from an ongoing open-label Phase 2 trial evaluating the efficacy and safety of autogene cevumeran in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated advanced melanoma. A Phase 2 clinical trial of autogene cevumeran in the adjuvant setting in patients with pancreatic ductal adenocarcinoma (PDAC) is planned to open in 2023....In 2023, BioNTech expects to provide a data update on the ongoing Phase 1/2 dose escalation and expansion, evaluating CLDN6 CAR-T cells with or without CLDN6 CARVac in patients with CLDN6-positive relapsed or refractory advanced solid tumors....The Company expects a Phase 2 study of BNT211 in patients with 2L+ platinum resistant testicular cancer to start in 2024."

New P2 trial • P1/2 data • P2 data • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Testicular Cancer

BNT211: A phase I/II trial to evaluate safety and efficacy of CLDN6 CAR-T cells and vaccine-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumors (SITC 2021) - P1/2 | "Manageable cytokine release syndrome (CRS, grade 1-2, the latter managed with Tocilizumab) without any signs of neurotoxicity have been observed in both patients of part 1 DL2. Updated data from open cohorts and especially for combination with CARVac will be presented. Clinicaltrials gov: NCT04503278"

CAR T-Cell Therapy • Late-breaking abstract • P1/2 data • Preclinical • Endometrial Cancer • Oncology • Ovarian Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CLDN6 • IL6

BNT211: A Phase I/II trial to evaluate safety and efficacy of CLDN6 CAR-T cells and CARVac-mediated in vivo expansion in patients with CLDN6+ advanced solid tumors (ESMO-IO 2021) - P1/2 | "Updated data from open cohorts will be presented. Clinical trial identification NCT04503278."

CAR T-Cell Therapy • Late-breaking abstract • P1/2 data • Preclinical • Genito-urinary Cancer • Oncology • Solid Tumor • Testicular Cancer • CLDN6 • IL6