ProAgio / ProDa BioTech - LARVOL DELTA

ProAgio in Combination With Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=51 | Recruiting | Sponsor: ProDa BioTech, LLC | Trial completion date: Oct 2026 ➔ Oct 2027 | Trial primary completion date: Jul 2026 ➔ Jul 2027

Trial completion date • Trial primary completion date • Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Reprogramming the pancreatic ductal adenocarcinoma microenvironment: a novel integrin-targeted cytotoxin, ProAgio, potentiates chemotherapy. (PubMed, Mol Cancer) - "These results confirm the novel mechanism of action of ProAgio, which includes reducing hypoxia and modulating TME. The current data provide evidence for potentiation of chemotherapy efficacy by ProAgio."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CAFs • CD4 • CD8 • CDH1 • HIF1A

ProAgio in Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: ProDa BioTech, LLC | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Apr 2026

First-in-human • Trial completion • Trial completion date • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

Combination of FOLFIRI (5-FU, Leucovorin, and Irinotecan) and ProAgio on colon cancer growth and metastasis (AACR 2024) - "Our study offers encouraging observations that ProAgio plus FOLFIRI can suppress colon cancer growth and metastasis by inhibiting αvβ3 preclinically and may provide a novel therapeutic combination for the management of colon cancers."

Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CAFs • CD8 • CD86 • CTLA4 • HAVCR2 • PD-1 • PRKDC

Project Cure CRC: advancing precision medicine in colorectal cancer through innovative research and targeted therapies (AACR 2025) - "Other projects investigate ProAgio, a protein targeting cells that support cancer survival, with the potential to improve therapies for hard-to-treat tumors... These initiatives demonstrate the Alliance's commitment to advancing precision medicine and addressing key gaps in CRC care, particularly for patients with treatment-resistant profiles. By funding high-impact research and fostering collaboration, Project Cure CRC aims to accelerate the development of personalized, effective treatments for CRC patients, transforming the landscape of colorectal cancer care."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • BRAF

ProAgio, a Novel Integrin αvβ3 Targeted Cytotoxin, Suppresses Tumor Growth and Reprograms the PDAC Microenvironment. (PubMed, bioRxiv) - P1 | "We have previously shown that the combination of GPH (gemcitabine, paricalcitol, and hydroxychloroquine) influences PDAC TME. Targeting integrin αvβ3 using ProAgio modulates the PDAC TME by improving perfusion, reducing hypoxia, reversing EMT, and alleviating immune suppression. ProAgio potentiates the effects of GPH therapy, which should be evaluated in future trials."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CAFs • CD4

ProAgio in Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P1 | N=46 | Recruiting | Sponsor: ProDa BioTech, LLC | N=28 ➔ 46

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

Trial of ProAgio in Advanced/Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=27 | Recruiting | Sponsor: University of Alabama at Birmingham | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

ProAgio in Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=58 | Active, not recruiting | Sponsor: ProDa BioTech, LLC | Recruiting ➔ Active, not recruiting | Trial primary completion date: May 2025 ➔ Oct 2025

Enrollment closed • Trial primary completion date • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

ProAgio in Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: ProDa BioTech, LLC | Trial completion date: Oct 2025 ➔ Jun 2028 | Trial primary completion date: Jul 2025 ➔ Jun 2027

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

ProAgio in Previously Treated Advanced Pancreatic Cancer and Other Solid Tumor Malignancies (clinicaltrials.gov) - P1 | N=58 | Recruiting | Sponsor: ProDa BioTech, LLC | Trial completion date: May 2025 ➔ Nov 2025

Trial completion date • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9

Trial of ProAgio in Advanced/Metastatic Colorectal Cancer (clinicaltrials.gov) - P1 | N=27 | Not yet recruiting | Sponsor: University of Alabama at Birmingham | Phase classification: P1/2 ➔ P1

Phase classification • Colorectal Cancer • Oncology • Solid Tumor

Trial of ProAgio in Advanced/metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=27 | Not yet recruiting | Sponsor: University of Alabama at Birmingham

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

ProAgio in Combination With Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=51 | Recruiting | Sponsor: ProDa BioTech, LLC | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Modulating Tumor Immunity by Targeting Tumor Fibrotic Stroma and Angiogenic Vessels for Lung Cancer Treatment. (PubMed, Cancers (Basel)) - "The depletion of dense fibrotic stroma (CAFs) by ProAgio decreases the Programmed Death Ligand 1 (PDL-1) levels in the stroma areas surrounding the tumors, and thus strongly increases the delivery of anti-PDL-1 antibody to the target cancer cells. The impact of ProAgio on tumor immunity provides strong synergistical effects of checkpoint inhibitors on lung cancer treatment."

Journal • Stroma • Fibrosis • Lung Cancer • Oncology • Solid Tumor • CAFs • CD4 • CD8

Depletion of Activated Hepatic Stellate Cells and Capillarized Liver Sinusoidal Endothelial Cells Using a Rationally Designed Protein for Nonalcoholic Steatohepatitis and Alcoholic Hepatitis Treatment. (PubMed, Int J Mol Sci) - "We report a strategy for NASH and AH treatment involving the induction of integrin αvβ3-mediated cell apoptosis using a rationally designed protein (ProAgio)...The reversal of sinusoid remodeling reduces the expression of leukocyte adhesion molecules on LSECs, thus decreasing leukocyte infiltration/activation in the diseased liver. Our studies present a novel and effective approach for NASH and AH treatment."

Journal • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Portal Hypertension

ProAgio in Combination With Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer (clinicaltrials.gov) - P1/2 | N=51 | Not yet recruiting | Sponsor: ProDa BioTech, LLC

Combination therapy • Metastases • New P1/2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer