To combat this, Lisata’s approach is to activate the C-end rule or CendR system, a naturally occurring active transport system to selectively deliver anticancer drugs through the stroma and into the tumor. Lisata’s lead product candidate, LSTA1, the recipient of multiple orphan designations, including for pancreatic cancer in both the United States and Europe as well as for malignant glioma in the United States is an investigational drug that actuates the CendR active transport mechanism while also having the potential to modify the tumor microenvironment and make it less immunosuppressive. LSTA1 targets tumor vascular endothelial cells as well as tumor cells themselves based on its affinity for alpha v beta 3 and beta 5 integrins that are selectively upregulated on these cells in comparison to healthy tissue.
LSTA1 is a non-amino acid cyclic internalizing RGD peptide that once founded these integrins is cleaved by proteases expressed in the tumor microenvironment to release a linear peptide fragment called a CendR fragment. The CendR fragment has high affinity for and then binds to an adjacent receptor called neuropilin-1, also upregulated on tumor vascular endothelial cells and tumor cells to activate the C-end Rule active transport pathway and ferry anticancer drugs more efficiently into solid tumors. Additionally, LSTA1 has been shown in a range of preclinical models to modify the tumor microenvironment, making it less hostile to immune cells, reducing tumor resistance to anticancer medications and impeding and/or preventing the metastatic cascade.
These results come internally from Lisata and from collaborators and research groups around the world and have been the subject of over 300 related scientific publications. Along with our collaborators, we also have amassed significant nonclinical data demonstrating enhanced delivery of a range of emerging anticancer therapies, including immunotherapies and RNA-based therapeutics. To-date, LSTA1 has demonstrated favorable safety, tolerability and activity to enhance delivery of standard of care chemotherapy for patients with metastatic pancreatic cancer. Our development programs are designed to exploit the potential of LSTA1 to enhance a variety of anticancer treatment modalities in a range of solid tumors. Currently, LSTA1 is the subject of about a dozen planned or active clinical trials globally for the treatment of very solid tumors.
Let me touch on a few of these individually. The ASCEND trial is a 155 patient double-blind, randomized, placebo-controlled clinical trial evaluating LSTA1 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma, also known as mPDAC. The trial is being conducted at up to 40 sites in Australia and New Zealand, led by the Australasian Gastro-Intestinal Clinical Trials Group, or AGITG in collaboration with the NHMRC clinical trial center at the University of Sydney. As previously reported in September, a positive outcome from the planned interim futility analysis was announced by the study’s independent Data Safety Monitoring Committee, which recommended continuation of the study without modification.
In addition, we are excited to report that full enrollment in Cohort A of ASCEND has been achieved and that overall enrollment in the study is now approximately 95% complete. With that, we now project to have top line data from Cohort A as early as the fourth quarter of next year, a full year earlier than originally anticipated. We plan to use the results of the ASCEND trial to explore possible conditional approvals in several jurisdictions and to design an optimized Phase III program in mPDAC. The BOLSTER trial is a Phase IIa, double-blind, placebo-controlled, multicenter, randomized basket trial with investigational sites planned in the United States, Europe, Canada and Asia, evaluating LSTA1 in combination with standards of care in advanced solid tumors, including head and neck, esophageal and cholangiocarcinoma.
This trial will include both cytotoxic and immunotherapy standards of care. As previously announced, patients have now been treated in the head and neck squamous cell carcinoma and cholangiocarcinoma cohorts and we expect a first patient in the esophageal cancer cohort by early next year. Cendifox, the Phase Ib/IIa open-label trial in the United States, evaluating LSTA1 in combination with neoadjuvant FOLFIRINOX-based therapies in pancreatic, colon and appendiceal cancers continues to make steady progress with approximately 80% of the overall target number of subjects in the study enrolled. We expect enrollment completion of the pancreatic cohort during the fourth quarter of this year and completion of the remaining two cohorts over the next two quarters with data readout in pancreatic cancer in late 2024.
