New York-based Graviton BioScience Corporation posted Phase Ib data for the selective ROCK2 inhibitor GV101, published in Signal Transduction and Targeted Therapy and announced on August 26. The molecule produced response rates in steroid-refractory chronic graft-versus-host disease (cGvHD) that the company said exceed published benchmarks for every currently approved therapy in the indication. The results, generated by Beijing Tide Pharmaceutical — which conducted the trial under the molecule's TDI01 designation — set up a Phase III randomized controlled trial that Graviton said it is now planning.
The open-label, multicenter Phase Ib/II trial enrolled 60 patients with moderate-to-severe cGvHD who had received one to five prior systemic therapies, with 30 patients sequentially assigned to each of the 200 mg and 400 mg daily cohorts. Through week 24, best overall response rates (bORR) were 86.2% (95% CI: 68.3–96.1) at 400mg and 67.9% (95% CI: 47.6–84.1) at 200mg. Failure-free survival (FFS) reached 89.4% and 78.6% respectively; median FFS was not reached. Overall survival was 96.6% at 400 mg and 100% at 200 mg, with one death attributed to COVID-19 pneumonia. Median time to first response was 30 days at 400 mg.
GV101 selectively inhibits ROCK2, a kinase that regulates Th17/Tfh cell differentiation, Treg activity, and fibrotic signaling — pathways central to both the inflammatory and fibrotic components of cGvHD.
The safety profile is notable for the absence of hematopoietic toxicity: no Grade ≥3 leukopenia, thrombocytopenia, or anemia, and no cytomegalovirus infections. The predominant Grade ≥3 treatment-related finding was bilirubin elevation, which Graviton attributed to reversible inhibition of UGT1A1 and OATP1B3 transporters rather than hepatocellular injury, and which was not accompanied by transaminase elevation.