BNT324 / DualityBio, BioNTech - LARVOL DELTA

Activity of BNT327/PM8002 (PD-L1 x VEGF-A bispecific antibody) in combination with BNT325/DB-1305 (TROP2 ADC) in solid tumors: Early preclinical and clinical evidence to support BNT327 + ADC combinations (AACR 2025) - P1/2 | "Emerging data suggest that IO-ADC combinations may lead to better patient outcomes. Early clinical data showed successful dose escalation allowing enrollment to NSCLC, TNBC, ovarian, and cervical cancer expansion cohorts, with updated clinical data planned to be presented. Further evaluation is ongoing of BNT327 with ADCs against HER2 (BNT323/DB-1303), B7H3 (BNT324/DB-1311) and HER3 (BNT326/YL202), with a focus on tumors where early monotherapy efficacy has been observed with these ADCs."

Combination therapy • IO biomarker • Preclinical • Breast Cancer • Cervical Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • B2M • CD276 • ERBB3 • HER-2

DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=440 | Not yet recruiting | Sponsor: DualityBio Inc.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

BioNTech Announces First Quarter 2025 Financial Results and Corporate Update (GlobeNewswire) - "Preliminary data from the ongoing Phase 1/2 clinical trial (NCT05914116) evaluating BNT324/DB-1311 in patients with advanced solid tumors, including patients with previously treated castration-resistant prostate cancer ('CRPC'), will be presented at the 2025 ASCO Annual Meeting."

P1/2 data • Castration-Resistant Prostate Cancer

DB‑1311/BNT324 (a novel B7H3 ADC) in patients with heavily pretreated castrate-resistant prostate cancer (CRPC). (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05914116 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276

DB-1311-O-1001: A Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=610 | Recruiting | Sponsor: DualityBio Inc. | N=450 ➔ 610

Enrollment change • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

Updated phase II efficacy and safety results of BNT327/PM8002 combined with paclitaxel as second-line (2L) therapy in small cell lung cancer (SCLC) (ELCC 2025) - P2 | "Funding: Biotheus Inc. BNT327 shows clinical activity as 2L treatment in SCLC, with adverse events consistent with chemo and IO treatment. Further evaluation in 2L SCLC is ongoing in a global phase II and a phase III trial in China and with BNT324/DB-1311, a B7H3 ADC, in a phase I/II study."

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276

A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer (clinicaltrials.gov) - P1/2 | N=594 | Not yet recruiting | Sponsor: BioNTech SE

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

BioNTech Announces Fourth Quarter and Full Year 2024 Financial Results and Corporate Update (GlobeNewswire) - "First clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating the combination of BNT327 and BNT325/DB-1305, a TROP2-targeted antibody-drug conjugate ('ADC') candidate, are planned to be published in 2025. Additional clinical trials exploring novel combinations of BNT327 with the ADC candidates BNT323/DB-1303 (trastuzumab pamirtecan) targeting HER2, BNT324/DB-1311 targeting B7-H3 or BNT326/YL202 targeting HER3 are planned to start in 2025."

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

BioNTech Provides Business and Pipeline Updates at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "A global randomized Phase 3 clinical trial evaluating BNT327/PM8002 in first line triple-negative breast cancer ('TNBC') is on track to start in 2025. Plan to initiate additional clinical trials exploring novel combinations of BNT327/PM8002 with ADCs BNT323/DB-1303 (trastuzumab pamirtecan), BNT324/DB-1311 and BNT326/YL202 in 2025. Plan to present first clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating BNT327/PM8002 plus BNT325/DB-1305 in multiple solid tumors in 2025. Plan to present clinical data from the ongoing global Phase 2 dose optimization trials evaluating BNT327/PM8002 plus chemotherapy in advanced TNBC (NCT06449222) and first line SCLC (NCT06449209) in 2025."

New P3 trial • New trial • P2 data • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

Duality Biologics and BioNTech Presented Positive Interim Data for Investigational B7-H3 Antibody-Drug Conjugate BNT324/DB-1311 in Advanced Solid Tumors at the ESMO Asia Congress 2024 (PRNewswire) - P1/2a | N=450 | NCT05914116 | Sponsor: DualityBio Inc. | "Among all evaluable patients with at least one post-baseline tumor assessment (n=238), the overall uORR was 32.4%, and the DCR was 82.4%. Among patients with SCLC (n=73), the uORR was 56.2%, and the DCR was 89.0%....Most patients with NSCLC had non-squamous histology (n=41), exhibiting an uORR of 22.0%, while patients with squamous NSCLC (n=25) had an uORR of 16.0%. Among patients with CRPC (n=32), BNT324/DB-1311 demonstrated early antitumor activity with an uORR of 28.0% and a DCR of 92.0%. With a median rPFS of 7.2 months, the rPFS data were not mature at the time of the analysis. The 6-month rPFS rate was 94.7%. In other tumor types, including cervical cancer (n=4), hepatocellular carcinoma (n=12), head and neck squamous carcinoma (n=3), and melanoma (n=11), BNT324/DB-1311 also exhibited antitumor activity with uORRs of 75.0%, 25.0%, 100.0%, and 36.4%, respectively."

P1/2 data • Castration-Resistant Prostate Cancer • Cervical Cancer • Hepatocellular Cancer • Melanoma • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

A phase I/II multicenter, first-in-human study of DB-1311/BNT324 (a novel B7H3 ADC) in patients with advanced solid tumors (ESMO Asia 2024) - P1/2 | "In pts with SCLC (n=33), unconfirmed ORR was 45.5% with higher ORR in pts without prior topotecan (56.0%, n=25) or prior IO (55.6%, n=9). PRs were also observed in 3 pts with CRPC, 3 pts with NSCLC and 1 pt with BTC. Conclusions DB-1311/BNT324 had a manageable safety profile with low rates of G≥3 hematological events and promising antitumor activity, particularly in pts with advanced/metastatic SCLC."

Clinical • Metastases • P1/2 data • Castration-Resistant Prostate Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • CD276

DB-1311-O-1001: A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=450 | Recruiting | Sponsor: DualityBio Inc. | N=280 ➔ 450 | Trial completion date: Apr 2025 ➔ Sep 2026 | Trial primary completion date: Apr 2025 ➔ Sep 2026

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

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

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

BioNTech and DualityBio Receive FDA Fast Track Designation for Antibody-Drug Conjugate Candidate BNT324/DB-1311 in Prostate Cancer (GlobeNewswire) - "BioNTech SE...and Duality Biologics...announced that the U.S. Food and Drug Administration ('FDA') granted Fast Track designation for BNT324/DB-1311 for the treatment of patients with advanced/unresectable, or metastatic castration-resistant prostate cancer ('CRPC') who have progressed on or after standard systemic regimens....The designation is based on preliminary safety and efficacy data from an ongoing Phase 1/2 trial with BNT324/DB-1311 in patients advanced or metastatic solid tumors."

Fast track • Metastatic Castration-Resistant Prostate Cancer

A phase 1/2a, multicenter, open-label, first-in-human study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of DB-1311 (a B7-H3-targeting ADC) in patients with advanced/metastatic solid tumors (AACR 2024) - P1/2 | "The study plans to enroll approximately 90 pts in Phase 1 and 190 in Phase 2a from locations including but not limited to Australia, United States, China, and Taiwan. To the data cut-off 05 Dec 2023, 11 pts have been enrolled in the study."

Clinical • IO biomarker • Metastases • P1/2 data • PK/PD data • Castration-Resistant Prostate Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • CD276

BioNTech to Present Clinical Data Updates for Personalized mRNA-based and Targeted Oncology Candidates at AACR 2024 (GlobeNewswire) - "Highlights of BioNTech’s clinical stage programs to be presented at AACR Annual Meeting 2024: Longer-term follow-up data of activity and immune responses of the investigator-initiated first-in-human Phase 1 trial (NCT04161755) with the mRNA-based individualized neoantigen-specific immunotherapy ('iNeST') candidate autogene cevumeran (BNT122, RO7198457) in patients with resected pancreatic ductal adenocarcinoma ('PDAC') will be presented....BioNTech will present preliminary results on the LuCa-MERIT-1 Phase 1 trial (NCT05142189) with its off-the-shelf, shared tumor-associated-antigen-based mRNA therapeutic cancer vaccine candidate BNT116 in combination with docetaxel in patients with advanced unresectable or metastatic non-small cell lung cancer ('NSCLC')."

P1 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

BioNTech to Present Clinical Data Updates for Personalized mRNA-based and Targeted Oncology Candidates at AACR 2024 (GlobeNewswire) - "BioNTech SE...will present clinical trial data for selected candidates from its oncology pipeline at the American Association for Cancer Research ('AACR') Annual Meeting 2024 in San Diego, California, from April 5-10, 2024. The oral and poster presentations will feature BioNTech’s investigational mRNA-based cancer vaccine and novel investigational antibody-drug conjugate ('ADC') approaches....A trial in progress poster will inform on the global Phase 1/2a trial (NCT05914116) of the topoisomerase-1 inhibitor-based ADC candidate BNT324/DB-1311 targeting the immune checkpoint protein B7H3 in patients with pretreated advanced or metastatic solid tumors....BioNTech is advancing the Company’s key programs into late-stage development with the aim to have ten or more potentially registrational trials in its oncology pipeline by the end of 2024."

New trial • Trial status • Oncology • Solid Tumor

A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=280 | Recruiting | Sponsor: DualityBio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

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

A Study of DB-1311 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=280 | Not yet recruiting | Sponsor: DualityBio Inc.

Metastases • New P1/2 trial • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

Preclinical development of a B7-H3-targeting ADC with a novel DNA topoisomerase I inhibitor for solid tumors (AACR 2023) - "B7-H3 targeting antibody-drug conjugates (ADCs), such as MGC018 and DS7300a, have shown preliminary clinical efficacy. DB-1311, a preclinical B7-H3 ADC candidate, with a DAR value of approximately 6, exhibited potent cytotoxicity in vitro and antitumor activity in vivo toward a range of B7-H3-expressing tumor cell lines representing several cancer types and was well tolerated in cynomolgus monkeys with promising pharmacokinetics characteristics. The preclinical antitumor activity and safety profile warrants further development of DB-1311 to evaluate its efficacy and safety in clinical studies."

Preclinical • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioma • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor

BioNTech and DualityBio Form Global Strategic Partnership to Accelerate Development of Differentiated Antibody-Drug Conjugate Therapeutics for Solid Tumors (GlobeNewswire) - "BioNTech SE...and Duality Biologics (Suzhou) Co. Ltd...announced that the companies have entered into exclusive license and collaboration agreements for two ADC assets to develop, manufacture and commercialize the two assets globally, excluding Mainland China, Hong Kong Special Administrative Region and Macau Special Administrative Region....As part of the collaboration, BioNTech will gain access to DualityBio’s lead candidate, DB-1303, which is a topoisomerase-1 inhibitor-based ADC directed against Human Epidermal Growth Factor Receptor 2 (HER2), a target that is overexpressed in a variety of cancers, which contributes to the aggressive growth and spread of cancer cells....BioNTech will also gain access to a second topoisomerase-1 inhibitor-based ADC candidate, DB-1311."

Licensing / partnership • Oncology • Solid Tumor