Phase I Clinical Testing of a First-in-Class Therapy against Metastatic Cancer

SUMMARY Metastatic disease is responsible for ~90% of cancer deaths and is the primary determinant in the life-limiting aspect of cancer. One validated driver of metastasis is miRNA-10b, a non-coding RNA associated with metastatic progression in numerous preclinical and > 100 clinical studies. Transcode has developed a novel therapeutic agent (termed MN-anti-miR10b and commercially developed as TTX-MC138) that relies on specific eradication of metastatic tumor cells. MN-anti-miR10b consists of antagomirs against miRNA-10b conjugated to a unique delivery platform, called TTX, which is optimized for the targeting of primary and metastatic tumor cells. Transcode’s proprietary and patented technology allows for the selective targeting of microRNA-10b in metastatic cells independent of their type or primary tumor origin. Numerous preclinical studies conducted by Transcode have shown that MN-anti-miR10b mediates significant miR-10b inhibition in vivo eliciting a marked and durable regression of lymph node and distant metastases in mouse models of breast cancer with no evidence of systemic toxicity. Specifically, as few as four to six weekly treatments with MN-anti-miR10b in combination with low dose chemotherapy led to complete regressions of detectable metastases. Of critical importance, following elimination of metastases and following discontinuation of therapy, no evidence was found to suggest recurrence over the remaining natural life span of the animals. In addition, similar studies in mouse models of pancreatic cancer were conducted with complete responses, defined as complete regression with no disease recurrence. Finally, initial evidence of safety and therapeutic activity was confirmed in companion cats with spontaneous metastatic breast cancer. TransCode has completed critical exploratory IND enabling studies in rats, dogs, and non-human primates with radiolabeled MN-anti-miR10b. Specifically, the information generated resulted in FDA authorization in support of an ongoing microdosing Phase 0 clinical trial in patients with advanced metastatic cancer. At this point, TransCode has conducted initial studies in patients, demonstrating delivery of the drug to metastatic lesions. The Phase 0 trial involves a single injection of a microdose of Cu-64 labeled MN-anti-miR10b which allows for direct visualization in vivo via PET-MR imaging, with a primary endpoint of determining the %ID/cc of the therapeutic that is delivered to the metastatic lesions. Based on the outcome of formal pIND communications with the FDA Office of Oncologic Diseases, the current application will support full IND-enabling studies, generation and filing of an IND application (Aim 1), as well as the Phase Ia dose-escalation trial in patients with advanced solid cancers (Aim 2). These funds will accelerate the program towards commercialization by enabling safety studies and potentially obtaining efficacy signals that could enable FDA approval of a first-in-class therapeutic against metastatic cancer of diverse primary disease origins.