Tomasz Jankowski, MD, PhD, on Non–Small Cell Lung Cancer: New Data on a Telomere-Targeting Agent

TIO represents a groundbreaking first-in-class, small molecule where directed targets telomeres in cancer cells. Specifically those telomeres positive with over 80% of all cancers, and approximately 78-83% of all non-small cell and cancer types being third positive. This innovative approach is particularly significant. TIO operates for a dual mechanism of action. Firstly, it targets telomeres by incorporating itself into newly synthesized telomeres, leading to chromatin uncapping, the generation of DNA damage signals and rapid apoptosis of cancer cells. Secondly, it has an immunogenic effect that enhances the body's immune response against the tumor. In preclinical models sequential treatment with TIO and immune checkpoint inhibitors has demonstrated potent and durable anti-tumor activity, for instance, in non-small cell lung cancer, combining TIO with atezolizumab resulted in a 60% complete response rate with an anti-cancer [inaudible 00:01:08]. In colorectal cancer achieved 100% complete responses with similar promising results in small cell and cancer as well as in hepatocellolar carcinoma. Turning our attention to the TIO-101 trial, it's a phase two dose optimization study for adult patients with advanced or metastatic non-small cell lung cancer who progress or relapse after one to four prior treatments, including immuno and platinum chemotherapy. Using assignment to stage design, 79 patients were assigned to receive one of three doses of TIO. 360, 180 or 60 milligrams, followed by semi-primab every three weeks for up to a year. The combination of TIO and semi-primab has been well tolerated by this heavily pre-treated patients. We have observed significant activity in this difficult to treat group, including both resistant to checkpoint inhibitors and chemotherapy. Importantly, the presence of TIO in circulating tumor cells has shown on target effects. In November, 2023, the ongoing phase two study identified with 180 milligram dose of TIO is the optimal dose, demonstrating better safety and superior efficacy compared to other doses. Specifically, only 9.8% of patients receiving 180 milligram dose reported grade three adverse events related to treatment with no grade four or five adverse events. Per safety profile suggests that TIO could potentially offer a far better alternative to chemotherapy. In terms of efficacy in the third line setting, disease control rate reached 85% for TIO with semi-primab comparing to 25-35% typically observed with standard chemotherapy. We have also seen long-term responses. With five patients having survival follow up for over 12 months, three of them are still on treatment. The median survey will follow up in the third line is 9.1 months. Moreover, overall response rate in the third line with dose 180 milligrams of TIO was 38%, comparing to about 6% for other treatment possibilities. In conclusion, the safety and efficacy achievements of TIO are truly promising. We are confirming many of the assumptions [inaudible 00:03:18] observed in the pre-clinical studies, and we are looking forward to follow up our patients.