Graviton BioScience Corporation Announces Publication of Positive Ph1b Trial Results for GV101 (TDI01) in Chronic Graft versus Host Disease in Signal Transduction and Targeted Therapy, by Beijing Tide Pharmaceutical

GV101, a novel, highly selective ROCK2 inhibitor, yielded an 86.2% best overall response rate (bORR) at 400 mg and a 67.9% bORR at 200 mg at 24 weeks in chronic Graft versus Host Disease (cGvHD) patients who had failed at least two prior lines of therapy. GV101's 24-week bORR exceeds published 6-month bORRs for all existing, approved steroid-refractory cGvHD therapies. Failure-free survival (FFS) was 83.9% at 24 weeks and reached 89.4% at 400 mg (78.6% at 200 mg); this FFS also exceeds published 6-month FFS probabilities for all approved steroid-refractory cGvHD therapies. Complete responses were observed in all but one organ system (only one participant had lower GI involvement). Favorable safety profile with no evidence of hematopoietic toxicity and no increased incidence of infections. The single Grade ≥3 adverse event occurring in ≥5% of participants was benign bilirubin elevation without transaminase elevation. This laboratory abnormality is related to reversible enzymatic (UGT1A1) and transporter (OATP1B3) inhibition by GV101. Graviton BioScience Corporation, a privately held, clinical-stage biotechnology company, announced the publication of peer-reviewed data from a multicenter Phase Ib/II multi-dose, open-label clinical trial evaluating the safety, tolerability, and efficacy of GV101 in patients with moderate to severe chronic Graft versus Host Disease (cGvHD). The data, published in Signal Transduction and Targeted Therapy, a Springer Nature Portfolio journal, provide efficacy and findings from the 60 enrolled patients, 30 at 200 mg and 30 at 400 mg, who had previously received one to five prior systemic therapies for cGvHD. Key efficacy results: At 24-weeks, GV101 yielded a bORR of 86.2% (95% CI: 68.3 to 96.1) at 400 mg and 67.9% (95% CI: 47.6 to 84.1) at 200 mg; FFS was 89.4% at 400 mg and 78.6% at 200 mg. Median FFS was not met at the time of analysis. OS was 96.6% at 400 mg and 100% at 200 mg; a single participant died, attributed to COVID-19 pneumonia. Median time to first response was 30.0 days (range 28-115 days) at 400 mg and 44.5 days (range 28-284 days) at 200 mg, consistent with a rapid onset. Median duration of response was not met at the time of analysis. Complete responses were observed in all organ systems except lower GI (only 1 participant had lower GI involvement). By 24-weeks, notable organ response rates included liver (52.6%), esophagus (50.0%), and upper gastrointestinal tract (50.0%); pulmonary response rate based on the 2014 NIH Consensus Criteria lung symptom score was 23.7% (95% CI: 11.4 to 40.2). Safety: AEs occurring in ≥20% of patients included transient bilirubin elevation (81.7%) and headache (23.3%). GV101-induced bilirubin elevations are benign, related to UGT1A1 inhibition (unconjugated) and OATP1B3 inhibition (conjugated), were generally transient and not associated with elevations in liver transaminases. Grade ≥3 TRAEs (reported in ≥5% of total patients) included only laboratory events: unconjugated bilirubin elevation (n = 10; 16.7%), total bilirubin elevation (n = 9; 15.0%), and conjugated bilirubin elevation (n = 3; 5.0%). There was no grade ≥3 leukopenia, thrombocytopenia, or anemia, and only one grade 3 neutropenia. There were no CMV infections. Graviton is currently in Phase III RCT planning for GV101 in cGvHD and plans to carry the high dose forward. About Chronic Graft versus Host Disease cGvHD is a rare, serious and potentially fatal complication of allogeneic stem cell transplantation that affects about 18,700 people in the US and has a global incidence of about 53,000 new cases per year. In cGvHD, donor immune cells attack healthy tissues and organs in the transplant recipient. The disease is characterized by persistent immune dysregulation, inflammation, and fibrosis that can affect multiple organ systems, significantly impair quality of life, and cause death. Despite advances in treatment, many patients experience inadequa...