BNT324 / DualityBio, BioNTech - LARVOL DELTA

DB-1311/BNT324 (a novel B7H3 ADC) in patients with advanced cervical cancer or platinum-resistant recurrent ovarian cancer (ESMO Asia 2025) - P1/2, P2 | "DB-1311/BNT324 showed encouraging efficacy in previously treated CC and PROC. The safety profile in these pts was manageable and consistent with previous reports. A phase 2 study of DB-1311/BNT324 plus pumitamig (BNT327, a PD-L1 x VEGF-A bsAb with activity in gynecological cancers; ASCO 2024 #5524) is currently enrolling pts with CC or PROC (DB-1311-201; NCT06953089)."

Clinical • Metastases • Platinum resistant • Castration-Resistant Prostate Cancer • Cervical Cancer • Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor • CD276 • PD-L1

DB-1311-O-1001: A Phase 1/2a Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=862 | Recruiting | Sponsor: DualityBio Inc. | Trial completion date: Jan 2028 ➔ May 2028 | Trial primary completion date: Sep 2027 ➔ Dec 2027

First-in-human • 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 • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

A phase II trial of DB-1311/BNT324 (B7H3 ADC) combined with BNT327 (PD-L1 x VEGF-A bsAb) or DB-1305/BNT325 (TROP2 ADC) in advanced/metastatic solid tumors (ESMO 2025) - P2 | "Funding DUALITYBIO INC. & BioNTech SE."

Metastases • P2 data • Cervical Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD276 • PD-L1 • VEGFA

Title: Early preclinical and clinical evidence to support the combination of BNT327 (PD-L1 x VEGF-A bispecific antibody) with antibody-drug conjugates (CICON 2025) - P1/2, P2 | "Preclinical data indicate that combining BNT327 with ADCs targeting TROP2, B7H3, HER2, or HER3 leads to superior anti-tumor effects compared to each drug alone. A manageable safety profile, with few overlapping toxicities and clinical activity, was observed in pts with PROC when treated with BNT327 plus the TROP2-ADC DB-1305/BNT325. Studies evaluating BNT327 with ADCs are enrolling: BNT323-03 (NCT06827236), BNT324-01 (NCT06892548), and DB-1311-201 (NCT06953089)."

Preclinical • Breast Cancer • Dental Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Solid Tumor • Stomatitis • Triple Negative Breast Cancer • CD276 • ERBB3 • HER-2

BNT324-01: A Phase 1b/2 Trial of BNT324/DB-1311 (B7H3 ADC) With BNT327 (PD-L1 x VEGF-A bsAb) in Lung Cancer (SCLC or NSCLC) (IASLC-WCLC 2025) - P1/2 | "Part 2 primary endpoint is safety and ORR in DO Cohorts 1&2 to determine the optimal dose, and ORR in Cohorts 3-7. Enrollment is ongoing."

IO biomarker • P1/2 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • PD-L1 • VEGFA

Recent advances in antibody-drug conjugates for metastatic castration-resistant prostate cancer. (PubMed, Zhejiang Da Xue Xue Bao Yi Xue Ban) - P3 | "Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 (dual PSMA/STEAP1-targeted), and DXC008 (dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, the B7-H3-targeted ADC ifinatamab deruxtecan has initiated..."

Journal • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • HER-2 • SLC44A4 • SLC4A4 • STEAP1

DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=492 | Recruiting | Sponsor: DualityBio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Phase Ib/II, multi-site, open-label, two-part trial to evaluate the efficacy, safety, pharmacokinetics, and recommended combination dose of BNT324 with BNT327 in participants with advanced lung cancer (ChiCTR) - P1/2 | N=594 | Not yet recruiting | Sponsor: Jilin Cancer Hospital; Jilin Cancer Hospital

New P1/2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • HER-2 • KRAS • NTRK • ROS1

DB-1311-O-1001: A Phase 1/2a Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=750 | Recruiting | Sponsor: DualityBio Inc. | Trial completion date: Sep 2026 ➔ Jan 2028 | Trial primary completion date: Sep 2026 ➔ Sep 2027

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 • Squamous Cell Carcinoma of Head and Neck • ALK • BRAF • CD276 • EGFR • KRAS • MET • NTRK1 • NTRK2 • NTRK3 • ROS1

DB‑1311/BNT324 (a novel B7H3 ADC) in patients with heavily pretreated castrate-resistant prostate cancer (CRPC). (ASCO 2025) - P1/2 | " This phase 1/2 study (NCT05914116) enrolled pts with advanced/metastatic solid tumors, including previously treated CRPC (post docetaxel/hormonal therapy). DB-1311/BNT324 showed encouraging efficacy and a manageable safety profile in heavily pretreated CRPC and is currently being evaluated in post Lu-177 CRPC and in taxane-naïve CRPC."

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

B7H3 ADC candidate DB-1311/BNT324 (PRNewswire) - P1/2a | N=610 | NCT05914116 | Sponsor: DualityBio Inc. | "Preliminary Data from...Clinical Trials with ADC Candidates were Presented Orally at the 2025 ASCO Annual Meeting....The data indicated early clinical activity and a manageable safety profile with low discontinuation rates. Most common adverse events were gastrointestinal and hematologic toxicities. In the 52 efficacy evaluable patients with heavily pretreated CRPC based on RCIST v1.1, the confirmed objective response rate (cORR) was 30.8%, DCR was 90.4%. Among 68 evaluable patients, the 6-month rPFS rate was 69.8%. Similar outcomes were observed across both dose levels (6 mg/kg or 9 mg/kg). Outcomes appeared better in earlier treatment lines and in patients who received one prior NHT, while antitumor activity was also observed in later lines and regardless of type of prior treatment or metastatic site."

P1/2 data • Castration-Resistant Prostate Cancer

BioNTech to Present Progress Across Diversified Oncology Pipeline at the 2025 ASCO Annual Meeting (The Manila Times) - "Data on BNT324/DB-1311, a B7H3-targeted ADC candidate, from an ongoing Phase 1/2 clinical trial...in patients with heavily pre-treated castration-resistant prostate cancer ('CRPC') will be presented during an oral session. The data indicated early clinical activity and a manageable safety profile."

P1/2 data • Castration-Resistant Prostate Cancer

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 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

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-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