mitazalimab (ADC-1013) / Alligator Biosci - LARVOL DELTA

CD40 agonist mitazalimab + mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Final efficacy analysis of the OPTIMIZE-1 study. (ASCO-GI 2026) - P1/2 | "Funded by Alligator Bioscience A.B. Clinical Trial Registration Number: NCT04888312 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

Alligator Bioscience announces publication of REACtiVe-2 Phase 1 trial data in Nature Communications (Alligator Bioscience Press Release) - "Key findings: The combination therapy significantly decreased intratumoral collagen content, likely through mitazalimab-mediated macrophage activation and stromal degradation. Treated tumors showed a clear rise in intratumoral T cells, indicating improved recruitment and immune access to the tumor....Patients with stable disease after prior chemotherapy achieved a median OS of 12.1 months and a 1-year survival rate of 50%."

P1 data • Pancreatic Ductal Adenocarcinoma

REACtiVe-2: phase I evaluation of dendritic cell vaccination and agonistic CD40 therapy following (m)FOLFIRINOX in metastatic pancreatic cancer. (PubMed, Nat Commun) - P1 | "In conclusion, MesoPher/mitazalimab combination therapy is safe and tolerable in patients with metastatic PDAC and enhances systemic immune activation and local immune responses. Future research should evaluate the efficacy of this promising approach as maintenance therapy shortly after completing chemotherapy."

Journal • P1 data • Immune Modulation • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40

Alligator Bioscience Presents New Data on Mitazalimab…at SITC 40th Anniversary Annual Meeting (ACCESS Newswire) - "The mitazalimab abstract presents new data from the OPTIMIZE-1 trial in metastatic pancreatic cancer....Key findings: (i) Improved survival outcomes at 6 months: PFS: 50.8% vs. 38.7%; OS: 89.5% vs. 69.4%; (ii) Manageable safety profile : Safety was manageable across both dose levels, with the increased rate of adverse events in the 900 μg/kg group attributed to extended treatment exposure; (iii) Biomarker analyses : Greater immune activation at 900 μg/kg, including higher levels of Ki67+ T cells, a marker of actively dividing and proliferating immune cells."

P1/2 data • Pancreatic Ductal Adenocarcinoma

CD40 agonist mitazalimab + mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma: dose characterization based on exposure response and biomarker analysis from the OPTIMIZE-1 study (SITC 2025) - "The analyses of safety endpoints suggest a higher probability of an event with higher exposure of mitazalimab, but this may be confounded by the combination treatment with mFOLFIRINOX.Conclusions The exposure-response data further supports mitazalimab contribution to the clinical benefits observed in OPTIMIZE-1. Based on available nonclinical and clinical mitazalimab data, a dose of 900 μg/kg is selected for the planned Phase 3 study.Ethics Approval OPTIMIZE-1 was single-arm, phase 1b/2 study conducted in 14 university hospitals in Belgium, France, and Spain according to the study protocol and amendments approved by local Institutional Review Boards and independent ethics committees, and in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines as defined by the International Conference on Harmonisation."

Biomarker • Clinical • IO biomarker • Metastases • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

Comparative Efficacy and Safety of Chemotherapeutic, Targeted, and Immunotherapy Drugs for Pancreatic Ductal Adenocarcinoma Treatment: A Network Meta-Analysis of RCTs (ACG 2025) - "Our analysis included 33 RCTs with a total sample size of 9,239 participants, comprising 5,636 in the treatment group and 3,603 in the control group. The included studies evaluated therapies such as Atezolizumab (79), Cabozantinib (76), Combined Chemotherapy (58), Demivistat + FOLFIRINOX (266), Durvalumab (3), EGPH20 + GEM-NABP (327), Erlotinib (518), FOLFIRINOX (433), Gemcitabine (2,090), Irinotecan (1,216), Mitazalimab (70), Nab-Paclitaxel (71), Nadunolimab (76), Napabucasin + GEM-NABP (565), Olaparib (124), Narilifox (766), Placebo (322), and Zenocutumab (454). The most significant survival benefit was observed with Irinotecan (OR = 4.96, 95% CI [1.45; 16.91],), while the least survival benefit was seen with Zenocutumab (OR = 0.38, 95% CI [0.03; 4.41],) compared to placebo."

Retrospective data • Novel Coronavirus Disease • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

REACtiVe-2: Phase I evaluation of dendritic cell vaccination and agonistic CD40 therapy following (m)FOLFIRINOX in metastatic pancreatic cancer (ESMO 2025) - P1 | "Conclusions In conclusion, MesoPher/mitazalimab combination therapy is safe and tolerable in patients with metastatic PDAC and enhances systemic immune activation and local immune responses. Future research should evaluate the efficacy of this promising approach with combination strategies as maintenance therapy shortly after completing systemic chemotherapy."

Metastases • P1 data • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD14 • CD40

CD40 agonist mitazalimab with mFOLFIRINOX in untreated metastatic pancreatic cancer: Biomarkers associated with outcomes from OPTIMIZE-1. (PubMed, Cell Rep Med) - P1/2 | "These results may inform future patient stratification strategies supporting a planned randomized confirmatory trial of mitazalimab with mFOLFIRINOX in mPDAC. This study was registered at ClinicalTrials.gov (NCT04888312)."

Biomarker • IO biomarker • Journal • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40

REACtiVe-2 Phase 1 data featuring mitazalimab demonstrate immune activation in metastatic pancreatic cancer – to be presented at ESMO 2025 (Alligator Bioscience Press Release) - "The investigator-sponsored trial...demonstrated that the combination of mitazalimab and Amphera’s dendritic cell vaccine MesoPher was safe and well-tolerated, with enhanced systemic and local immune responses. Half of the patients achieved stable disease after three administrations, with post-treatment biopsies revealing increased tumor-infiltrating T cells and reduced collagen deposition."

P1 data • Pancreatic Cancer

OPTIMIZE-1: Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Pancreatic Cancer Patients (clinicaltrials.gov) - P1/2 | N=94 | Active, not recruiting | Sponsor: Alligator Bioscience AB | Trial primary completion date: Jan 2024 ➔ Jun 2026

Trial primary completion date • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Alligator announces publication of OPTIMIZE-1 biomarker analysis in Cell Reports Medicine supporting mitazalimab and mFOLFIRINOX in metastatic pancreatic cancer (Alligator Bioscience Press Release) - "The OPTIMIZE-1 study met its primary endpoint, with a confirmed objective response rate of 42.1% in the Phase 2 cohort. Median duration of response was 12.6 months, progression-free survival 7.7 months, and overall survival 14.9 months. The survival rate at 24 months was 29.4%, triple that of chemotherapy alone....Baseline expression of a tumor-intrinsic fibrotic gene signature, directly linked to the mode of action of mitazalimab, was associated with improved overall survival."

Biomarker • P1/2 data • Pancreatic Ductal Adenocarcinoma

Alligator Bioscience announces acceptance of two abstracts at SITC 40th Anniversary Annual Meeting (Alligator Bioscience Press Release) - "The presentations will feature new data from Alligator’s pipeline programs mitazalimab and ATOR-4066."

Clinical data • Pancreatic Ductal Adenocarcinoma

IGNITE: Maintenance Combinatorial Myeloid Immunotherapy for Unresectable Pancreatic Cancer (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: University of Pennsylvania

New P2 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Alligator announces final 30-month OPTIMIZE-1 results highlighting the potential of mitazalimab in metastatic pancreatic cancer (Alligator Bioscience Press Release) - "After a median follow-up of 33 months, two patients remained on treatment and 8 in long-term survival follow up resulting in a 30-month overall survival (OS) rate of 21%. The final readout confirms data maturity, demonstrating both primary and secondary efficacy endpoints that compare favorably with historical controls. As previously reported, the objective response rate (ORR) was 54.4% (42.1% confirmed). The median duration of response was 12.6 months, with a median progression-free survival (PFS) of 7.8 months."

P2 data • Pancreatic Cancer

Grant awarded to investigator-initiated Phase 2/3 trial with mitazalimab in biliary tract cancer (Alligator Bioscience Press Release) - "It is expected to enroll its first patient in the second quarter of 2026, with the initial part of the study enrolling a total of 112 patients across 30 sites in France."

Financing • New P2/3 trial • Biliary Tract Cancer

Alligator Bioscience announces upcoming presentation of REACtiVe-2 Phase 1 data at ESMO Congress 2025 (Alligator Bioscience Press Release) - "Alligator Bioscience...announces that data from the Phase 1 REACtiVe-2 trial (NCT05650918) of the CD40 agonist mitazalimab in combination with dendritic cell vaccination (Amphera’s MesoPher) will be presented at the European Society for Medical Oncology (ESMO) Congress 2025....The study, led by Erasmus MC Cancer Institute, evaluated the safety, tolerability, and immunologic activity of mitazalimab in combination with MesoPher following chemotherapy with mFOLFIRINOX in patients with metastatic pancreatic cancer. The data will be presented in a poster entitled 'REACtiVe-2: Phase I Evaluation of Dendritic Cell Vaccination and Agonistic CD40 Therapy Following (m)FOLFIRINOX in Metastatic Pancreatic Cancer'."

P1 data • Pancreatic Cancer

CD40 agonist mitazalimab + mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): 24-month follow up and dose characterization from the OPTIMIZE-1 study (ESMO-GI 2025) - P1/2 | "Mitazalimab (900 μg/kg) in combination with mFFX continues to demonstrate clinically meaningful survival benefits when compared to historical controls. The safety and efficacy results observed after further characterization of the 450 μg/kg dose level support the selection of 900 μg/kg as recommended phase 3 dose. Table: 265P Dose characterization efficacy outcomes 1Follow-up was restricted to a maximum of 3 scans or 7 months."

Clinical • Metastases • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CD40

Alligator to present 24-month OPTIMIZE-1 data at ESMO GI 2025 (Alligator Bioscience Press Release) - P1b/2 | N=94 | OPTIMIZE-1 (NCT04888312) | Sponsor: Alligator Bioscience AB | "Alligator Bioscience...announced that new data from the ongoing OPTIMIZE-1 study...will be presented at the ESMO Gastrointestinal Cancers Congress 2025....The poster includes 24-month efficacy results and dose characterization data from OPTIMIZE-1 (NCT04888312), a Phase 1b/2 trial in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC). Patients receiving 900 μg/kg mitazalimab showed a median overall survival of 14.9 months and a median progression-free survival of 7.8 months, supporting a sustained clinical benefit. The survival rate at 24 months was 29.4%, triple that of chemotherapy alone. A comparison between the 900 μg/kg and 450 μg/kg cohorts revealed a higher response rate for 900 μg/kg of 54.4% versus 22.7%."

P1/2 data • Pancreatic Ductal Adenocarcinoma

Alligator Receives Positive Scientific Advice from EMA on Phase 3 Trial of Mitazalimab (ACCESSWIRE) - "Alligator Bioscience...announced that the European Medicines Agency (EMA) has provided positive scientific advice supporting the overall design of the planned Phase 3 study of mitazalimab in metastatic pancreatic cancer. The advice confirms that the proposed Phase 3 study of mitazalimab in combination with mFOLFIRINOX is appropriately designed to support future marketing authorization application. The guidance confirms that the information submitted supports mitazalimab advancement to registrational trials, and Alligator is continuing preparations for trial initiation in line with regulatory input."

European regulatory • Pancreatic Cancer

Alligator Bioscience Receives FDA Endorsement of Mitazalimab Phase 3 Dose for Pancreatic Cancer (ACCESSWIRE) - "Alligator Bioscience...announced that the U.S. Food and Drug Administration (FDA) has provided feedback supporting the selection of the 900 µg/kg dose of its CD40 agonist mitazalimab for the planned Phase 3 study in metastatic pancreatic ductal adenocarcinoma (mPDAC)."

FDA event • Pancreatic Ductal Adenocarcinoma

Biomarker data from Alligator Bioscience’s OPTIMIZE-1 trial presented at ASCO 2025 Annual Meeting (Alligator Bioscience Press Release) - P1/2 | N=94 | OPTIMIZE-1 (NCT04888312) | Sponsor: Alligator Bioscience AB | "The study has demonstrated strong clinical outcomes to date, including a ~30% survival rate at 24 months and a median overall survival of 14.9 months...The biomarker analyses highlighted mitazalimab’s immunological mechanism of action, with immune activation in responding patients and gene signatures associated with clinical benefit and improved survival. These results support continued development of mitazalimab, including a planned confirmatory trial in mPDAC."

Biomarker • P1/2 data • Pancreatic Ductal Adenocarcinoma

Biomarkers associated with outcomes from OPTIMIZE-1: CD40 agonist mitazalimab with mFOLFIRINOX in patients with untreated metastatic pancreatic cancer. (ASCO 2025) - P1/2 | "A potentially predictive fibrosis-related gene signature, directly linked to mitazalimab's mode of action, was associated with improved OS. Biomarker correlations further suggest a mitazalimab-driven contribution to clinical benefits in the OPTIMIZE-1 trial. These encouraging results will inform the planned randomized confirmatory trial of mitazalimab in combination with mFFX in mPDAC."

Biomarker • Clinical • IO biomarker • Metastases • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD40 • KRAS

Alligator Bioscience Announces Paediatric Study Waiver for Mitazalimab Granted by the European Medicines Agency (Yahoo Finance) - "Alligator Bioscience...announced that the European Medicines Agency (EMA) has granted a waiver from conducting paediatric clinical trials for Alligator's lead asset mitazalimab. The waiver, issued as part of the Paediatric Investigation Plan (PIP) regulatory process, exempts Alligator from the obligation to conduct pediatric studies with mitazalimab in the treatment of pancreatic cancer. This regulatory milestone removes a key requirement ahead of potential future marketing authorization submissions in the European Union."

European regulatory • Pancreatic Cancer

Alligator Bioscience to attend ASCO 2025 Annual Meeting (Alligator Bioscience Press Release) - "Alligator Bioscience...is pleased to announce that data from its OPTIMIZE-1 clinical trial will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentation, titled 'Biomarkers associated with outcomes from OPTIMIZE-1: CD40 agonist mitazalimab with mFOLFIRINOX in patients with untreated metastatic pancreatic cancer', will take place during the Developmental Therapeutics-Immunotherapy session, focusing on tissue-based biomarkers."

Biomarker • P1/2 data • Pancreatic Cancer

Alligator Bioscience Completes Phase 3 GMP Manufacturing of Mitazalimab, Remains on Track for Trial Initiation with Partner (ACCESSWIRE) - "Alligator Bioscience...today announced the successful completion of the manufacture of the first GMP drug product batch of its lead asset mitazalimab using a new improved commercial-scale manufacturing process. The material is intended for the planned Phase 3 trial in first line metastatic pancreatic cancer. The batch was produced at Thermo Fisher Scientific, a global leader in pharmaceutical manufacturing. This key milestone underpins the Phase 3 readiness of mitazalimab."

Commercial • Pancreatic Cancer