gotistobart (BNT316) / OncoC4, BioNTech - LARVOL DELTA

Phase 1 study of gotistobart (BNT316/ONC-392) in combination with lutetium Lu 177 vipivotide tetraxetan (Lu 177) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO 2025) - P1/2 | "With known limitations in sample size during dose escalation, gotistobart in combination with Lu 177 demonstrated a manageable safety profile and promising preliminary PSA50 rates in patients with mCRPC during the dose escalation phase. Overall findings support combination regimens with gotistobart doses less than 10 mg/kg in the ongoing Phase 2 randomized dose optimization study."

Clinical • Combination therapy • Metastases • P1 data • Castration-Resistant Prostate Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Immunology • Oncology • Prostate Cancer • Solid Tumor

Dose escalation of next generation Anti-CTLA-4 antibody ONC-392 in combination with fixed dose of pembrolizumab in patients with advanced solid tumors (SITC 2022) - P1a/1b | "Eleven patients had prior anti-PD-1/PD-L1 and 5 melanoma patients had prior ipilimumab. The rate of irAE is low relative to drugs of the same class. These results support the feasibility to significantly increase drug exposure for full immunotherapeutic potential of anti-CTLA-4 and anti-PD-1 combination therapy."

Clinical • Combination therapy • Cervical Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

PRESERVE-003: ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors (clinicaltrials.gov) - P3 | N=630 | Recruiting | Sponsor: OncoC4, Inc. | Trial completion date: Jun 2027 ➔ Aug 2028 | Trial primary completion date: Jun 2026 ➔ Aug 2027

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTLA4 • LAG3 • TIGIT

Anti-Tumor Activity of Gotistobart Compared to Docetaxel in Patients with Metastatic Squamous Non-Small Cell Lung Cancer (sqNSCLC) Progressing on PD-(L)1 Inhibitors: Stage 1 PRESERVE-003 Phase 3 Trial (ELCC 2026) - No abstract available

Clinical • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Updated efficacy results from the phase 1 study of gotistobart (BNT316/ONC-392) in combination with lutetium Lu 177 vipivotide tetraxetan (Lu 177) in patients with metastatic castration-resistant prostate cancer (mCRPC). (ASCO-GU 2026) - P1/2 | "Clinical Trial Registry Number: NCT05682443. The full, final text of this abstract will be available on Feb 23 at 05:00 PM EST."

Clinical • Combination therapy • Metastases • P1 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

A randomized, phase II, dose optimization of gotistobart, a pH-sensitive anti-CTLA-4, in combination with standard dose pembrolizumab in platinum-resistant recurrent ovarian cancer: Safety, efficacy and dose optimization (PRESERVE-004/GOG-3081) (ESMO 2024) - P2 | "Early results show encouraging safety and clinical activity in PROC patients receiving gotistobart + pembrolizumab."

Clinical • Combination therapy • Late-breaking abstract • P2 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Peritoneal Cancer

Safety and clinical activity of target-preserving anti-CTLA-4 antibody ONC-392 as monotherapy in NSCLC patients who progressed on PD(L)1-targeted immunotherapy. (ASCO 2023) - P1a/1b, P3 | "Overall, ONC-392 monotherapy with 10 mg/kg is safe and tolerable. Onc-392 monotherapy has showed encouraging anti-tumor activity in IO-resistant NSCLC when compared with historical data. Based on these encouraging data, we have initiated a Phase 3 study testing ONC-392 monotherapy among NSCLC who progressed on PD(L)1-targeting immunotherapy (NCT05671510)."

Clinical • Monotherapy • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Nephrology • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • Squamous Cell Carcinoma

Gotistobart: “Gotistobart phase 3 data show survival benefit in CPI-treated squamous NSCLC”; Non-small cell lung cancer (BioNTech, 44th Annual J.P. Morgan Healthcare Conference) - “PRESERVE-003 trial stage 1 data: gotistobart1 reduces risk of death by 54% compared with docetaxel”

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Gotistobart: Pivotal data from P3 PRESERVE-003 trial (NCT05671510) for metastatic NSCLC in 2026 (BioNTech, 44th Annual J.P. Morgan Healthcare Conference)

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Gotistobart: “Gotistobart phase 3 data show survival benefit in CPI-treated squamous NSCLC”; Non-small cell lung cancer (BioNTech, 44th Annual J.P. Morgan Healthcare Conference) - “PRESERVE-003 trial stage 1 data: gotistobart1 reduces risk of death by 54% compared with docetaxel”

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Gotistobart: Pivotal data from P3 PRESERVE-003 trial (NCT05671510) for metastatic NSCLC in 2026 (BioNTech, 44th Annual J.P. Morgan Healthcare Conference)

P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology

BioNTech and OncoC4 Receive FDA Orphan Drug Designation for Gotistobart in Squamous Non-Small Cell Lung Cancer (BioNTech Press Release) - "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."

Orphan drug • Trial status • Lung Non-Small Cell Squamous Cancer

BioNTech Provides Strategic Business Update and Outlines 2026 Areas of Focus at 44th Annual J.P. Morgan Healthcare Conference (The Manila Times) - "Expected 2026 oncology milestones include seven late-stage data readouts...Additional late-stage trial readouts through 2030+ set to create multiple launch opportunities across tumor types, building BioNTech into a multi-product oncology company."

Clinical data • New P3 trial • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Hepatocellular Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

BioNTech and OncoC4 Announce Clinically Meaningful Overall Survival Benefit for Selective Treg Modulator Gotistobart in Patients with Previously Treated Squamous Non-Small Cell Lung Cancer (GlobeNewswire) - "Data from the non-pivotal stage of the trial are being presented today in an oral presentation at the IASLC ASCO 2025 North America Conference on Lung Cancer....At the data cut-off on August 8, 2025, 87 patients with sqNSCLC had been randomized....At a median follow-up of 14.5 months, patients in the gotistobart treatment arm had not yet reached the median OS, while the docetaxel treatment arm achieved a median OS of 10 months. The data showed that the gotistobart arm reduced the risk of death by 54% compared to the docetaxel treatment arm (HR=0.46, 95% CI: 0.25–0.84; nominal p-value 0.0102)."

P3 data • Non Small Cell Lung Cancer

PRESERVE-006: ONC-392 Plus Lutetium Lu 177 Vipivotide Tetraxetan in Patients With mCRPC (clinicaltrials.gov) - P1/2 | N=148 | Active, not recruiting | Sponsor: OncoC4, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

OncoC4 announced…that China's National Medical Product Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for gotistobart (BNT316/ONC392) for the treatment of patients with squamous non-small cell lung cancer (sqNSCLC) who have progressed on prior standard immuno-oncology therapies (IO) (PRNewswire) - "The NMPA's BTD designation is based on the Stage 1 safety and efficacy data of the PRESERVE-003 trial. The detailed data will be reported in an upcoming medical conference in December 2025."

Breakthrough therapy • P3 data • Lung Non-Small Cell Squamous Cancer

PRESERVE-003: A Phase 3 Study of Gotistobart Versus Docetaxel in Metastatic NSCLC After Progression on PD-(L)1 Inhibitors (IASLC-WCLC 2025) - P3 | "While CTLA-4 is a recognized immunotherapy target in solid tumors, no current anti-CTLA-4 antibodies, including ipilimumab and tremelimumab have demonstrated efficacy as monotherapies to date in NSCLC. Kaplan-Meier estimates of median OS will be presented by treatment arm, along with two-sided 95% CIs. Secondary endpoints include objective response rate and progression-free survival based on RECIST 1.1, and safety."

IO biomarker • Metastases • P3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Solid Tumor • PD-1

Trial Design for Next-Generation CTLA-4 Antibody Gotistobart Monotherapy Being Co-Developed with BioNTech in NSCLC at the IASLC 2025 World Conference on Lung Cancer (GlobeNewswire) - "The presentation will feature the pivotal trial Stage II design for PRESERVE-003 (NCT05671510), a two-stage, randomized, open-label, active-controlled Phase 3 Study evaluating gotistobart monotherapy compared to docetaxel in squamous non-small cell lung cancer (sqNSCLC) after progression on a PD-(L)1 inhibitor."

Clinical protocol • Lung Non-Small Cell Squamous Cancer

PRESERVE-004: ONC-392 and Pembrolizumab in Platinum Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=58 | Active, not recruiting | Sponsor: OncoC4, Inc. | Trial primary completion date: Jun 2025 ➔ Oct 2025

Platinum resistant • Trial primary completion date • Fallopian Tube Cancer • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers that Progressed on PD-1/PD-L1 Inhibitors (ChiCTR) - P3 | N=600 | Recruiting | Sponsor: Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences); Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sci

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • LAG3 • TIGIT

Gotistobart in combination with pembrolizumab in patients with advanced melanoma who have progressed on PD-1 inhibitors with or without CTLA-4 inhibitors. (ASCO 2025) - P1/2 | "Gotistobart is a pH-sensitive anti-CTLA-4 mAb and we hypothesized that gotistobart in combination with pembrolizumab (pembro) could improve outcomes for ipilimumab plus nivolumab (ipi/nivo) treatment failure. Gotistobart 3 mg/kg or 6 mg/kg plus pembro 200 mg, Q3W, provided durable response and clinically meaningful OS benefit, regardless of prior ipi treatment, with nearly half of patients being next-treatment free at one year follow up. To our knowledge, this is one of the largest cohorts ever studied in patients with advanced melanoma R/R to ipi/nivo."

Clinical • Combination therapy • IO biomarker • Metastases • Gastroenterology • Gastrointestinal Disorder • Immunology • Melanoma • Oncology • Solid Tumor • BRAF

Early Results Show Improved Survival Rates in Patients with Metastatic Prostate Cancer (NYU Langone Health) - P1/2 | N=141 | PRESERVE-006 (NCT05682443) | Sponsor: OncoC4, Inc. | "The early findings from 24 patients showed the drug combination was generally well tolerated, with most side effects rated as mild to moderate. Trial participants who received lower doses saw promising reductions in PSA levels—a key marker of prostate cancer activity—suggesting the treatment may be effective. These results support moving forward with a phase 2 trial to optimize dosing and further evaluate benefits for patients."

P1 data • Prostate Cancer

BioNTech to Present Progress Across Diversified Oncology Pipeline at the 2025 ASCO Annual Meeting (The Manila Times) - "Preliminary data on BNT316/ONC-392 (gotistobart)...from two ongoing Phase 1/2 clinical trials evaluating the antibody candidate in combination with current standard of care treatments will be presented. Data from the PRESERVE-001 clinical trial...in patients with advanced melanoma indicated a manageable safety profile and early signs of anti-tumor activity....Data from the PRESERVE-006 clinical trial...in patients with metastatic CRPC indicated a manageable safety profile and preliminary efficacy."

P1/2 data • Castration-Resistant Prostate Cancer • Melanoma

PRESERVE-001: Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC (clinicaltrials.gov) - P1/2 | N=733 | Active, not recruiting | Sponsor: OncoC4, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Adenoid Cystic Carcinoma • Breast Cancer • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Renal Cell Carcinoma • Salivary Gland Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer

LuCa-MERIT-1: Clinical Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=220 | Recruiting | Sponsor: BioNTech SE | N=160 ➔ 220 | Trial completion date: Nov 2028 ➔ Nov 2031 | Trial primary completion date: Apr 2027 ➔ Feb 2030

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor