pumitamig (BNT327) / BioNTech, BMS - LARVOL DELTA

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

Dual PD-L1 blockade and VEGF-A neutralization with the Fc-silenced bispecific antibody BNT327 (pumitamig) shows potent antitumor activity in preclinical models (CICON 2025) - "Antitumor activity was more pronounced than that of single PD-1 (pembrolizumab) or PD-L1 (atezolizumab) checkpoint inhibitor treatment. The safety and efficacy of BNT327 is being investigated in multiple clinical trials, including Phase II and Phase III trials investigating the combination with chemotherapeutic agents in triple-negative breast cancer and lung cancer. Phase I/II trials investigating the combination of BNT327 with antibody-drug conjugates have also been initiated."

IO biomarker • Preclinical • Breast Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8

Short talk | Dual PD-L1 blockade and VEGF-A neutralization with the Fc-silenced bispecific antibody BNT327 shows potent antitumor activity in preclinical models (CICON 2025) - No abstract available

Preclinical • Oncology

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) - No abstract available

Metastases • P2 data • Oncology • Solid Tumor • CD276 • PD-L1 • VEGFA

BNT323-03: A Phase 1/2 trial of BNT323/DB-1303 (HER2 ADC) with BNT327 (PD-L1 x VEGF-A) in patients (pts) with advanced breast cancer (BC) (ESMO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • VEGFA

BNT327-03: Safety and Effectiveness of BNT327, an Investigational Therapy in Combination With Chemotherapy for Patients With Untreated Small-cell Lung Cancer (clinicaltrials.gov) - P3 | N=439 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Global Phase 2 Randomized Trial of BNT327 (Pumitamig; PD-L1 x VEGF-A bsAb) + Chemotherapy for 1L ES-SCLC: Dose Optimization Analysis (IASLC-WCLC 2025) - P2 | "Methods : In this global Phase 2, randomized, open-label,parallel group trial (NCT06449209), patients with treatment-naïve ES-SCLC received pumitamig+etoposide+carboplatin x 4 cycles followed by pumitamigmaintenance (Cohort 1); patients progressing after 1L or 2L treatment received pumitamig+paclitaxel(Cohort 2) or pumitamig+topotecan (Cohort 3). Pumitamig plus etoposide/carboplatin showed encouraging efficacy and acceptable safety in 1L ES-SCLC. This first presentation in a global population of a bispecific antibody targeting checkpoint inhibition and angiogenesis confirms the encouraging data previously reported in the 1L SCLC Chinese study (https://doi.org/10.1016/S1556-0864(25)00494-0).This dose optimization study supports further development of pumitamig in 1L SCLC,currently being evaluated in the ROSETTA Lung-01 Phase 3 trial."

Clinical • P2 data • Cardiovascular • Hypertension • Lung Cancer • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • PD-L1

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

BNT314-02: A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment BNT327 and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=482 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

A Clinical Study to Test if an Investigational Treatment Called BNT314 When Used in Combination With Another Investigational Treatment BNT327 and Chemotherapy, is Beneficial and Safe for Patients With Advanced Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=482 | Not yet recruiting | Sponsor: BioNTech SE

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

ROSETTA Breast-01: The Effects and Safety of Pumitamig in Patients With Triple-Negative Breast Cancer (clinicaltrials.gov) - P3 | N=558 | Not yet recruiting | Sponsor: BioNTech SE

New P3 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

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

BNT326-01: A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors (clinicaltrials.gov) - P1/2 | N=550 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Oncology • Solid Tumor

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

A First-in-human, Dose Escalation and Indication Expansion Study of BNT3212 as Monotherapy or in Combination With BNT327 in Adults With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=375 | Not yet recruiting | Sponsor: BioNTech SE

Monotherapy • New P1/2 trial • Solid Tumor

BNT326-02: A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=420 | Not yet recruiting | Sponsor: BioNTech SE

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

BNT327-02: Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: BioNTech SE | N=70 ➔ 100 | Trial completion date: Sep 2028 ➔ Jun 2029 | Trial primary completion date: Nov 2027 ➔ Aug 2028

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

PM8002 (BNT327) in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Biotheus Inc.

New P2 trial • pMMR • Colorectal Cancer • Oncology • Solid Tumor

First Disclosure of Global Interim Phase 2 Data for BioNTech and Bristol Myers Squibb PD-L1xVEGF-A Bispecific Antibody Pumitamig (BNT327/BMS986545) in Patients with Extensive-Stage Small Cell Lung Cancer Shows Encouraging Antitumor Activity (GlobeNewswire) - "The data are being presented today as a late-breaker oral presentation at the IASLC 2025 World Conference on Lung Cancer....Global interim Phase 2 data showed a 76.3% confirmed objective response rate (cORR), 100% disease control rate (DCR), a median progression free survival (mPFS) of 6.8 months and a manageable safety profile."

Late-breaking abstract • P2 data • Small Cell Lung Cancer

A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors (clinicaltrials.gov) - P1/2 | N=550 | Not yet recruiting | Sponsor: BioNTech SE

New P1/2 trial • Oncology • Solid Tumor

A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=380 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Sep 2032 ➔ May 2029

Trial completion date • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

BioNTech receives FDA orphan drug designation for lung cancer treatment (Investing.com) - "H.C. Wainwright maintained its Buy rating and $138.00 price target on BioNTech...stock after the company received Orphan Drug Designation from the FDA....designation was granted for BioNTech’s bispecific antibody treatment for small cell lung cancer (SCLC), which appears to be BNT327, also known as PM8002, according to the FDA’s Orphan Drug product website."

Orphan drug • Stock price • Small Cell Lung Cancer

First report of efficacy and safety results from a phase 2 trial evaluating BNT327/PM8002 plus chemotherapy (chemo) as first-line treatment (1L) in unresectable malignant mesothelioma. (ASCO 2025) - P2 | " After a safety run-in (n=6), this ongoing, multicenter, single-arm phase 2 clinical trial recruited chemo naive pts (pts) aged ≥18 yrs with unresectable malignant mesothelioma (pleural (MPM) or peritoneal (MPeM)) to evaluate BNT327 30 mg/kg Q3W IV combined with 4-6 cycles pemetrexed and platinum, followed by BNT327 maintenance. BNT327 plus chemo as a 1L regimen for mesothelioma showed encouraging efficacy, including in tumors of epithelioid histology. AEs were consistent with those expected for the treatment regimen."

Clinical • P2 data • Anemia • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • Thoracic Cancer

A global phase 2/3, randomized, open-label trial of BNT327/PM8002 in combination with chemotherapy (chemo) in first-line (1L) non-small cell lung cancer (NSCLC). (ASCO 2025) - P2/3 | "In the Phase 3 part, pts will be randomized 1:1 to receive BNT327 at the selected dose (based on the Phase 2 part) plus chemo (carboplatin + pemetrexed for Substudy A, carboplatin + paclitaxel for Substudy B) or pembrolizumab 200 mg plus chemo Q3W IV, followed by Q3W IV maintenance BNT327 or pembrolizumab (both with maintenance pemetrexed for Substudy A). Secondary endpoints include duration of response, disease control rate (Phase 2), PFS per investigator, ORR, landmark PFS and OS, patient reported outcomes and occurrence of AEs, and rates of dose interruption, reduction and discontinuation due to TEAEs (Phase 3); with efficacy endpoints per RECIST 1.1; safety per CTCAE v5.0. The trial is enrolling."

Clinical • Combination therapy • IO biomarker • P2/3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A global phase III, double-blind, randomized trial of BNT327/PM8002 plus chemotherapy (chemo) compared to atezolizumab plus chemo in patients (pts) with first-line (1L) extensive-stage small cell lung cancer (ES-SCLC). (ASCO 2025) - P3 | "Preliminary results from a Phase II trial showed encouraging efficacy results and a manageable safety profile for BNT327 with paclitaxel as second-line (2L) treatment of pts with SCLC (1992P, ESMO 2023)...Pts will be initially randomized 1:1:1 to receive combination therapy of atezolizumab (1,200 mg IV) plus chemo (etoposide + carboplatin) (Arm 1), BNT327 (2,000 mg IV) plus chemo (Arm 2), or BNT327 (1,400 mg IV) plus chemo (Arm 3) administered Q3W for four cycles, followed by maintenance therapy with atezolizumab (Arm 1) or BNT327 (Arm 2 and Arm 3) Q3W until confirmed disease progression, intolerable toxicity, participant withdrawal, trial termination or up to two years, whichever occurs first...Secondary endpoints include progression-free survival (PFS), objective response rate, PFS rates and OS rates at defined timepoints, patient-reported outcomes, occurrence of treatment emergent adverse event (TEAEs) and occurrence of dose delay, infusion interruption, and..."

Clinical • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor