BNT324/DB-1311 showed encouraging antitumor activity and a manageable safety profile in a Phase 1/2a clinical trial in heavily pretreated patients with locally advanced or metastatic solid tumors, including small cell lung cancer ("SCLC"), non-small cell lung cancer ("NSCLC"), and castration-resistant prostate cancer ("CRPC").

•        In patients with SCLC with at least one post-baseline tumor assessment and who had received prior immunotherapy but no prior topoisomerase 1 inhibitor, the unconfirmed objective response rate ("uORR") was 70.4% at the BNT324/DB-1311 9 mg/kg dose level.

•        In patients with CRPC, the uORR was 28.0%; imaging progression-free survival ("rPFS") data are not yet mature, with a median rPFS of 7.2 months and a 6-month rPFS rate of 94.7%.

•        Multiple clinical trials combining selected assets from BioNTech's and DualityBio's strategic partnership with BNT327/PM8002, an investigational bispecific antibody targeting PD-L1 and VEGF-A, are planned; a Phase 1/2 trial evaluating BNT324/DB-1311 with BNT327/PM8002 in patients with SCLC or NSCLC is planned to start in 2025.

SHANGHAI and SUZHOU, China, Dec. 5, 2024 -- Duality Biologics ("DualityBio") today announced first data from a global Phase 1/2a clinical trial (NCT05914116, CTR20232835) evaluating BNT324/DB-1311, an investigational next-generation antibody-drug conjugate ("ADC") targeting the transmembrane glycoprotein B7-H3. The data were presented in an oral session at the 2024 European Society of Medical Oncology Asia Annual Meeting ("ESMO Asia") in Singapore and showed encouraging antitumor activity alongside a manageable safety profile in heavily pretreated patients with locally advanced or metastatic solid tumors. BNT324/DB-1311 is being co-developed by BioNTech SE (Nasdaq: BNTX, "BioNTech") and DualityBio.

The analysis of the ongoing Phase 1/2a trial included 277 participants across various solid tumor types including small cell lung cancer ("SCLC"), non-small cell lung cancer ("NSCLC"), castration-resistant prostate cancer ("CRPC"), and squamous cell carcinoma of the head and neck ("SCCHN"). About 75% of participants had an Eastern Cooperative Oncology Group ("ECOG") performance status of 1, and approximately 61% had undergone two or more lines of therapy. The primary endpoints of the trial are safety and objective response rate ("ORR") as determined by investigator. The secondary endpoints include duration of response ("DoR"), disease control rate ("DCR"), progression-free survival ("PFS"), overall survival ("OS") among others. The data showed the following results:

•        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%. The majority of patients with SCLC received 6 mg/kg and 9 mg/kg of BNT324/DB-1311, with no difference in uORR between the two dose groups (54.5% and 58.8%, respectively). Notably, at the 9 mg/kg dose level, the uORR in patients with SCLC who had prior immunotherapy but no treatment with topoisomerase I inhibitors reached 70.4%.

•        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.

•        BNT324/DB-1311 showed a manageable safety profile across all evaluated patients and tumor types (n=277). The most common treatment-related adverse events (TRAEs) reported included nausea, neutrophil count decreased, anemia, white blood cell count decreased, decreased appetite, and platelet count decreased.

Dr. John Zhu, Founder and CEO of Duality Biologics, said, "BNT324/DB-1311 is an innovative ADC molecule co-developed by BioNTech and DualityBio, showing clinical data in the study phase. This early data supports DualityBio's ADC technology platform, and the continued research and development of novel ADC therapies with the aim to improve the standard of care, and embodying DualityBio's commitment to exploring innovative treatments while advancing the global ADC industry for patient benefit."

BNT324/DB-1311 is one of three clinical stage ADC candidates in BioNTech's and DualityBio's global strategic partnership aimed at advancing these novel ADC assets into late-stage development in multiple high unmet medical need cancer indications. Multiple clinical trials combining selected assets from BioNTech's and DualityBio's strategic partnership with BNT327/PM8002, a novel investigational bispecific antibody targeting PD-L1 and VEGF-A, which is being jointly developed by BioNTech and Biotheus are planned in various solid tumor indications. A Phase 1/2 clinical trial evaluating the combination of BNT325/DB-1305, a TROP2 targeting ADC candidate, and BNT327/PM8002 is currently ongoing. A Phase 1/2 trial evaluating BNT324/DB-1311 in combination with BNT327/PM8002 in patients with SCLC or NSCLC is planned to start in 2025.

About BNT324/DB-1311

BNT324/DB-1311 is a next-generation topoisomerase-I-inhibitor-based ADC candidate targeting the immune checkpoint protein B7-H3. The transmembrane glycoprotein B7-H3 plays a critical role in the anti-tumor immune response and the shaping of the tumor microenvironment. It is overexpressed in a range of solid tumors, with limited expression in healthy tissues, and has been associated with disease progression and very poor prognosis.^[i] Preclinical studies have shown that BNT324/DB-1311 exhibits antitumor activity in various solid tumor models.^[ii] Preliminary data from the ongoing Phase 1/2a trial (NCT05914116) has demonstrated antitumor activity and a manageable safety profile for BNT324/DB-1311 in patients with advanced solid tumors.

In June 2024, 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"). In July 2024, the FDA granted Orphan Drug Designation to BNT324/DB-1311 for the treatment of advanced or metastatic esophageal squamous cell carcinoma.

About Duality Biologics

Duality Biologics ("DualityBio") is a clinical-stage biotech company focusing on the discovery and development of next-generation antibody-drug conjugate (ADC) therapeutics to treat cancer, autoimmune diseases, and beyond. DualityBio has successfully built several cutting-edge ADC technology platforms with global intellectual property rights. Based on deep understanding of diseases, DualityBio has built a robust pipeline of ADCs, including several candidates in clinical stage. DualityBio has seven ongoing global multi-regional clinical trials (MRCTs) across 17 countries with over 1,000 patients enrolled. In addition, DualityBio is leveraging its novel protein engineering and unique ADC technologies to develop the next generation of "Super ADCs", such as bispecific ADCs, ADCs with novel MOA payload and antibody-immune modulator-conjugates.