On January 12, 2026 BioNTech SE (Nasdaq: BNTX, "BioNTech") and OncoC4, Inc. ("OncoC4") reported that the U.S. Food and Drug Administration ("FDA") has granted Orphan Drug Designation to gotistobart (also known as BNT316 or ONC-392) for the treatment of squamous NSCLC, an aggressive subtype of lung cancer with limited therapeutic options in the advanced stage. The FDA grants Orphan Drug Designation to potential new medicines for prevention, diagnosis, or treatment of patients with either a rare disease, or a specific patient population with a non-rare disease. This designation underscores the urgent medical need for new therapeutic options for patients living with this condition.
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Gotistobart is a novel tumor microenvironment-selective regulatory T cell ("Treg") depletion candidate targeting CTLA-4. With its unique mode of action, gotistobart has the potential to address the high unmet medical need in patients with squamous NSCLC, which accounts for around 25% of all lung cancer cases1 and high disease-related mortality2. Squamous NSCLC is a devastating disease with a 5-year relative survival rate of 15%, a median survival time of 11 months in the United States (2000-2017)3, and with limited treatment options in the advanced stage. For advanced or metastatic squamous NSCLC patients, the treatment options for second-line therapy after first-line immunotherapy and chemotherapy are usually limited to chemotherapy or palliative therapy.4
The pivotal Phase 3 clinical trial PRESERVE-003 (NCT05671510; EUCT:2023-505311-20-01) is ongoing, evaluating gotistobart in patients with metastatic squamous NSCLC at 160 sites globally. In a data readout from the non-pivotal dose-confirmation stage of the trial, gotistobart demonstrated a clinically meaningful overall survival ("OS") benefit, compared to standard-of-care chemotherapy and a manageable safety profile in squamous NSCLC patients whose disease had progressed following anti-PD-(L)1 therapy and platinum-based chemotherapy. These data were previously announced and presented in an oral presentation at the IASLC ASCO (Free ASCO Whitepaper) 2025 North America Conference on Lung Cancer. In addition to the recently granted Orphan Drug Designation, the FDA granted Fast Track Designation to gotistobart in 2022 for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy.
About gotistobart (BNT316/ONC-392)
Gotistobart (BNT316/ONC-392) is a tumor microenvironment-selective Treg depletion candidate developed jointly by BioNTech and OncoC4. As a pH-sensitive monoclonal antibody, gotistobart is designed to enable CTLA-4 protein recycling. After binding to the CTLA-4 receptor on the cell surface, the complex is internalized, and the pH change causes the antibody to unbind, allowing CTLA-4 to return to the surface to preserve the immune checkpoint function at peripheral organs and to enhance anti-tumor immunity in the tumor microenvironment5. Gotistobart is currently in late-stage clinical development as monotherapy and as a component of combination therapy in various cancer indications. Gotistobart received Fast Track Designation from the U.S. Food and Drug Administration ("FDA") in 2022 for the treatment of patients with metastatic NSCLC whose disease progressed on prior anti-PD-(L)1 therapy and Breakthrough Therapy Designation from China’s National Medical Products Administration ("NMPA") in 2025.
About PRESERVE-003 Trial
PRESERVE-003 (NCT05671510; EUCT:2023-505311-20-01) is a two-stage, open-label Phase 3 trial evaluating the efficacy and safety of gotistobart as monotherapy compared to the standard-of-care chemotherapy (docetaxel) in sqNSCLC patients, who have progressed on PD-(L)1 inhibitors and platinum-based chemotherapy. The non-pivotal stage of the trial originally included all NSCLC patients. The ongoing pivotal stage is currently enrolling patients with squamous NSCLC. During the ongoing pivotal stage, patients are planned to be enrolled at 160 clinical sites in various countries and regions, including Australia, Belgium, Canada, China, Germany, Italy, the Netherlands, Spain, South Korea, Türkiye, the United Kingdom and the United States. The primary endpoint is overall survival. Secondary endpoints include overall response rate, progression-free survival and safety profile.
(Press release, BioNTech, JAN 12, 2026, View Source [SID1234661940])