TriSalus Life Sciences® Inc., with MedTech Acquisition Corporation announced additional Phase 1 clinical data presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting taking place in Chicago, Illinois, from June 2-6, 2023. TriSalus' ongoing Phase 1 Pressure-Enabled Regional Immuno-Oncology (PERIO-01) (NCT04935229) clinical study for uveal melanoma with liver metastases (UMLM) is studying an investigational class C toll-like receptor-9 agonist, SD-101, delivered intravascularly by TriSalus' TriNav® Infusion System (TriNav) using the Company's proprietary Pressure-Enabled Drug Delivery™ (PEDD) method of administration. PERIO-01 is evaluating whether this platform approach can improve the performance of systemic checkpoint inhibitors in patients with UMLM.

Pharmacokinetic data indicate that the strategy of delivering a toll-like receptor-9 agonist with the PEDD method results in high drug levels in the liver, while the drug is undetectable after four hours in the serum in 97% of patients with available data. The immune effects in liver metastases and the blood are consistent with broad tumor microenvironment modulation and the ability of SD-101 to deplete myeloid derived suppressor cells (MDSCs) in the liver. PERIO-01 is an open-label, first-in-human Phase 1 trial of SD-101, administered by hepatic arterial infusion with TriNav using PEDD in UMLM.

The study consists of dose-escalation cohorts of SD-101 (2, 4, or 8 mg) alone or with immune checkpoint inhibition. At the data cutoff as of May 12, 2023, 39 patients were enrolled in the PERIO-01 trial, with each having received at least one dose of SD-101. Of the patients with available data, five patients were treatment-naïve and 81% had failed at least one prior line of therapy, including three patients on their sixth-line of treatment.

Following receipt of SD-101, patients demonstrated a statistically significant expansion of peripheral natural killer cells, along with evidence of decreased expression of exhaustion markers on these cells. Increases in serum cytokines, including IFNg and IL-18, also supported systemic immune activation. Additionally, decreased levels of ctDNA levels were observed within eight out of 13 evaluable patients.

Stable disease was noted as the best on-treatment response for target lesions in 15 out of 25 patients, with one partial response. These findings, along with reductions of intratumoral MDSCs and decreases in ARG-1 (arginase 1) and IDO-1 (indoleamine 2,3-dioxygenase-1) gene levels, support the hypothesis that SD-101 delivered via PEDD may have favorable immune effects within the liver and systemically. Overall, the data emerging from the PERIO-01 trial continues to indicate immunologic changes are occurring within the liver, with decreases in ctDNA and disease control observed across a group of heavily pre-treated patients with UMLM, as well as a low treatment-related serious adverse event rate.