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 | "Mitazalimab (900 µg/kg) in combination with mFFX continues to show clinically meaningful survival benefits compared with historical controls. Together with a promising duration of response and encouraging long-term survival rates in previously untreated mPDAC patients, these findings support the continued development of mitazalimab in a confirmatory Phase 3 study. Efficacy outcomes."

Clinical • IO biomarker • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • 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

Evaluating the relative treatment efficacy of CD40 agonist mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) using unanchored indirect treatment comparisons (ITCs). (ASCO-GI 2025) - P1 | "Literature based ITCs show a significantly better efficacy of mitazalimab + mFFX versus the current available therapies in patients with mPDAC. These trends will have to be confirmed in a randomized Phase 3 study. 1."

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

Efficacy and safety of mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): An interim analysis of the optimize-1 phase 1b/2 study. (ASCO 2023) - P1b/2 | "OPTIMIZE-1 (NCT04888312) is a Phase 1b/2, open label, multicenter study designed to evaluate safety, tolerability, and efficacy of mitazalimab in combination with mFOLFIRINOX (Oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2, 5-FU 2.4 g/m2) in patients (pts) with previously untreated mPDAC... Mitazalimab + mFOLFIRINOX is a feasible regimen with a manageable safety profile. Mitazalimab administered at 900 µg/kg in combination with mFOLFIRINOX shows encouraging antitumor activity in mPDAC, meriting continued development. The study passes futility and continues to full accrual."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Acute Kidney Injury • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Immune Modulation • Infectious Disease • Nephrology • Neutropenia • Oncology • Pain • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Pneumonia • Renal Disease • Respiratory Diseases • CD40 • IFNG

CD40 agonist mitazalimab combined with mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Primary analysis of the OPTIMIZE-1 phase Ib/II study (ESMO-GI 2024) - P1/2 | "The OPTIMIZE-1 study met its primary endpoint, with a manageable safety profile and promising DoR associated with a clinically meaningful survival benefit. Furthermore, the NKT & T cell activation profile is strongly suggestive of mitazalimab's contribution to deep anti-tumor responses. These encouraging results warrant continued development in a randomized phase 3 study."

Clinical • IO biomarker • Metastases • P1/2 data • Tumor mutational burden • Anemia • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Thrombocytopenia • CD40 • CD8 • TMB

Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre phase 1b/2 study. (PubMed, Lancet Oncol) - P1/2 | "Mitazalimab with mFOLFIRINOX demonstrated manageable safety and encouraging activity, warranting continued development in a phase 3, randomised, controlled trial. The results from OPTIMIZE-1 pave the way for further exploration and confirmation of a novel immunotherapy treatment regimen for metastatic pancreatic ductal adenocarcinoma, which is a complex and aggressive cancer with very low survival rates and restricted treatment options."

Journal • Metastases • P1/2 data • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Thrombocytopenia • CD40

Window Study of Intratumoral Mitazalimab in Breast Cancer (WINIT-BC) (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: Jennifer Zhang

New P1 trial • Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Alligator Bioscience…announced that new data from its Phase 1b/2 OPTIMIZE-1 study evaluating mitazalimab in combination with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC) will be presented at the ASCO Gastrointestinal Cancers Symposium (ASCO GI)… (Alligator Bioscience Press Release) - "The presentation will highlight new analyses from OPTIMIZE-1 further characterizing the clinical benefit observed with mitazalimab plus standard chemotherapy in metastatic pancreatic cancer."

P1/2 data • Pancreatic Ductal Adenocarcinoma

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

Enrollment open • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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

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