Phase 2 Study Outcomes: TPN-101 for PSP, ALS, and FTD

Biotechnology firm Transposon Therapeutics has reported promising findings from its Phase 2 clinical trial of TPN-101, a potential treatment for progressive supranuclear palsy (PSP). The drug was found to reduce levels of neurofilament light chain (NfL) and interleukin 6 (IL-6), significant biomarkers for neurodegeneration and neuroinflammation respectively in PSP. Notably, TPN-101 was the first to achieve this in PSP treatment.
The study involved participants who received TPN-101 for the full 48-week duration, exhibiting a stabilization of clinical symptoms as measured by the PSP Rating Scale (PSPRS). This was in contrast to those on a placebo whose condition continued to deteriorate. The drug's effects on biomarkers were observed as early as the first 24 weeks, suggesting a possible 24-week delay before clinical benefits are noticeable.
Dr. Adam Boxer, the principal investigator of the study, highlighted the lack of effective treatments for PSP, a uniformly fatal disease with a similar prevalence to ALS. He underscored the significance of TPN-101's impact on CSF NfL concentrations and other biomarkers, which have not been previously observed in PSP trials.
In addition to PSP, TPN-101 demonstrated positive effects on biomarkers in a Phase 2 study involving patients with ALS and frontotemporal dementia (FTD) related to the C9orf72 gene. The drug showed improvements in vital capacity, a respiratory measure linked to ALS patient mortality. The study also indicated that TPN-101 could potentially treat Alzheimer's disease, as it targets dysregulation of retrotransposable elements, a factor in several neurodegenerative diseases.
Transposon Therapeutics plans to progress TPN-101 into a Phase 3 study for PSP and expand its development to include Alzheimer's disease. The company's founder, Dr. Eckard Weber, emphasized the importance of these findings, stating they provide the first evidence that neurodegenerative diseases involving LINE-1 dysregulation can be treated with a specific inhibitor.
The Phase 2 PSP study was a randomized, double-blind, placebo-controlled, parallel-group trial with 42 participants. It included a 6-week screening period, a 24-week double-blind treatment period, a 24-week open-label treatment period, and a follow-up visit 4 weeks post-treatment. The Phase 2 study in C9orf72-related ALS/FTD followed a similar structure with 42 participants.
TPN-101 works by inhibiting the LINE-1 reverse transcriptase, which when dysregulated, can lead to overproduction of LINE-1 DNA and contribute to neurodegenerative and autoimmune diseases. PSP is a rare, fatal condition with no approved treatments, primarily affecting individuals in their mid-to-late 60s. ALS and FTD are also serious neurodegenerative diseases with limited treatment options.
Transposon Therapeutics is a clinical-stage biopharmaceutical company focused on developing novel therapies for neurodegenerative and aging-related diseases, with TPN-101 as its lead compound. The company also has a robust pipeline of therapies for additional conditions.