BNT327 / BioNTech - LARVOL DELTA

Dual PD-L1 blockade and VEGF-A neutralization with the bispecific antibody BNT327/PM8002 shows potent antitumor activity in preclinical models (AACR 2025) - "Antitumor activity was dose-dependent where tested, and superior to single PD-1 (pembrolizumab) or PD-L1 (atezolizumab) checkpoint inhibitor treatment. In conclusion, BNT327 inhibits PD-1/PD-L1 signaling and VEGF-A/VEGFR2 signaling in vitro and shows potent antitumor activity in vivo both in syngeneic and xenograft models. The safety and efficacy of BNT327 as a monotherapy or in combination is being investigated in multiple clinical trials in patients with solid tumors, including Phase II and Phase III trials investigating the combination with chemotherapeutic agents in triple-negative breast cancer and lung cancer."

Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • IFNG • IL2

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

Discovery of HX016-7, a novel PD-L1 x VEGF BsAb, as a new candidate treatment of solid tumors (AACR 2025) - "A first-in-class PD-L1xVEGF bispecific antibody (BsAb), BNT327/PM8002, has demonstrated promising efficacy in treating TNBC and NSCLC cancers in advance stage of clinical development, which prompted us to engineer a novel and potentially best-in-class (BIC) PD-L1xVEGF BsAb by using a validated anti-PD-L1 and a novel anti-VEGF (HX006, a novel VEGF mAb with more favor activity over Avastin) mAb sequences. In a subcutaneous A549 non-small-cell lung cancer (NSCLC) cell-derived xenograft model in immunocompromised mice, HX016-7 also showed slightly stronger anti-tumor activity over BNT327/PM8002, which can be attributed to anti-VEGF function. We believe these preclinical data warrants the candidacy of HX016-7 to be further developed for the treatment of solid tumors."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Study of PM8002 (Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With NSCLC (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: Biotheus Inc. | Phase classification: P2/3 ➔ P2 | N=374 ➔ 64 | Trial primary completion date: Mar 2025 ➔ Sep 2024

Enrollment change • Phase classification • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BNT327 With Chemotherapy Elicits Strong Results in ES-SCLC (Targeted Oncology) - P2 | N=50 | NCT05844150 | Sponsor: Biotheus Inc. | "The PD-L1 and VEGF-A bispecific antibody BNT327 demonstrated encouraging clinical activity and had a tolerable safety profile when combined with chemotherapy as a first-line treatment in extensive-stage small cell lung cancer (ES-SCLC), according to a phase 2 trial (NCT05844150) presented at the 2025 European Lung Cancer Congress (ELCC)....The median treatment exposure was 5.7 months (95% CI, 4.4-7.2). At a median follow-up of 14.5 months (95% CI, 13.4-15.3), the confirmed overall response rate (ORR) was 85.4% (95% CI, 72.2%-93.9%) and the unconfirmed ORR was 87.5% (95% CI, 74.8%-95.3%). The disease control rate (DCR) was 97.9% (95% CI, 88.9%-100%). The 6-month and 12-month OS rates were 91.7% (95% CI, 79.3%-96.8%) and 72.7% (95% CI, 57.6%-83.1%), respectively. The median OS was not yet mature."

P2 data • Small Cell Lung Cancer

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

Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy Following Chemoimmunotherapy (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

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

Phase 2 study of the efficacy and safety of BNT327/PM8002 plus systemic chemotherapy as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC) (ELCC 2025) - P2 | "Combined targeting of PD-L1 and angiogenesis with chemotherapy may enhance anti-tumor immune responses vs standard of care.We present data from an ongoing phase II study of BNT327, an investigational bispecific antibody targeting PD-L1 and VEGF-A, plus chemotherapy in first-line ES-SCLC. This open label, single arm, multicenter phase II study (NCT05844150) recruited pts aged ≥18 years with ECOG PS 0-1 with histologically or cytologically confirmed SCLC who had not received systemic treatment for ES-SCLC, to evaluate tumor responses per RECIST 1.1 and safety per CTCAE v5.0 of 30 mg/kg Q3W BNT327 plus platinum-etoposide administered Q3W for 4 cycles, followed by BNT327 Q3W until disease progression or unacceptable toxicity. As of 21 Nov 2023, 50 pts had been enrolled (median age 59 years, range 46–75, 80% ECOG 1). BNT327 plus platinum-based chemotherapy as a first-line treatment for ES-SCLC showed encouraging efficacy and an acceptable tolerability profile and is..."

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

PM8002 in Combination With Chemotherapy as First Line Therapy in Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Biotheus Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatocellular Cancer • Oncology • Solid Tumor

A Study of PM8002 (Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With ES-SCLC (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Biotheus Inc. | Recruiting ➔ Active, not recruiting | Phase classification: P2/3 ➔ P2 | N=445 ➔ 50 | Trial primary completion date: Jun 2025 ➔ May 2024

Enrollment change • Enrollment closed • Phase classification • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

PM8002-B004C-TNBC-R: A Study of PM8002 Plus Nab-paclitaxel as First Line Therapy for TNBC (clinicaltrials.gov) - P1/2 | N=42 | Active, not recruiting | Sponsor: Biotheus Inc. | Recruiting ➔ Active, not recruiting | N=60 ➔ 42

Enrollment change • Enrollment closed • Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR

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 Announces Fourth Quarter and Full Year 2024 Financial Results and Corporate Update (GlobeNewswire) - "A global randomized Phase 3 clinical trial evaluating BNT327 in first-line TNBC is on track to start in 2025. Data from the ongoing global Phase 2 dose optimization clinical trials evaluating BNT327 in combination with chemotherapy in first-line small cell lung cancer ('SCLC') (BNT327-01, NCT06449209) and TNBC (BNT327-02, NCT06449222) are planned to be published in 2025. Data from two Phase 2 clinical trials conducted in China in first- and second-line SCLC (NCT05844150, NCT05879068, respectively) are expected to be presented at the European Lung Cancer Congress ('ELCC') taking place March 26-29, 2025 in Paris, France."

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

BNT327-01: Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: BioNTech SE | Recruiting ➔ Active, not recruiting

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

Neoadjuvant Chemotherapy Combined With Bispecific Antibody Versus Monoclonal Antibody in Locally Advanced NSCLC (clinicaltrials.gov) - P2 | N=160 | Not yet recruiting | Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy Following Chemoimmunotherapy (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: BioNTech SE

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety, Effectiveness, and Pharmacokinetics of BNT327 in Combination With Chemotherapy and Other Investigational Agents for Lung Cancer (clinicaltrials.gov) - P2/3 | N=982 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

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

Biomis announced that PM8002 (anti-PD-L1/VEGF dual antibody) was successfully included in the “Breakthrough Therapy List“ (Biotheus Press Release) - "...PM8002 has passed the review of the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) and was successfully included in the 'Breakthrough Therapy List'. The indication is PM8002 injection combined with albumin-bound paclitaxel as the first-line treatment for inoperable locally advanced/recurrent metastatic triple-negative breast cancer (TNBC)."

Breakthrough therapy • Triple Negative Breast Cancer

BioNTech Completes Acquisition of Biotheus (GlobeNewswire) - "BioNTech SE...announced today the completion of the acquisition of Biotheus...The acquisition was announced on November 2024 and builds on the successful collaboration on the late-stage clinical asset BNT327, an investigational bispecific antibody targeting PD-L1 and VEGF-A, and other bispecific antibody candidates. The transaction is part of BioNTech’s oncology strategy, aimed at expanding the Company’s capabilities to research, develop and commercialize BNT327 as a pan-tumor technology platform for combination therapies. With this completion of the acquisition, BioNTech obtains full global rights to BNT327 and rights to all other candidates of Biotheus’ pipeline as well as to its in-house antibody generation platform and bispecific antibody drug conjugate capability."

Diagnostic • M&A • 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=320 | Not yet recruiting | Sponsor: BioNTech SE

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

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

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

BNT327: Data from P2 trial (NCT06449209) for 1L SCLC in 2025 or later (BioNTech, 43rd Annual J.P. Morgan Healthcare Conference) - Data from P2 trial (NCT06449222) for 1L/2L TNBC in 2025 or later

P2 data • Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Triple Negative Breast Cancer

BNT327: Data from P2 trial (NCT06449209) for 1L SCLC in 2025 or later (BioNTech, 43rd Annual J.P. Morgan Healthcare Conference) - Data from P2 trial (NCT06449222) for 1L/2L TNBC in 2025 or later

P2 data • Breast Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Triple Negative Breast Cancer

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