Introduction
This Proof-of-Concept multi-centre study assessed safety and efficacy of a novel Cathepsin-K inhibitor, VBX-1000, in canine patients with periodontitis.

Method
Twenty dogs with periodontal disease were orally treated with 25 mg/kg and 50 mg/kg once-a-day for 60 days. If treatment was well tolerated, dogs were then treated with 50 mg/kg up to Day-90. The primary objective was to assess the effects of VBX-1000 on plasma CTX1 (pCTX1 = marker of bone resorption). Other objectives included evolution of Clinical Attachment Loss (CAL), Periodontal Probing Depth (PPD), and alveolar bone defect measured by X-ray radiography (n=20 dogs) and CBCT scan (n=10 dogs).

Results
VBX-1000 was well tolerated. At Day-60, pCTX1 in both groups was similarly reduced compared to baseline (p<0.05). At Day-90, in the entire population (n=20), pCTX1 plasma was 0.10±0.04 vs 0.27±0.23 ng/mL at baseline (p<0.001). Radiographs before and after treatment showed a significant decrease in width (n=60 teeth; 3 teeth/dog; p<0.0001) and depth (p<0.05) of the bone defect between the root of the tooth and the maxillary bone. Such effects on bone defect was confirmed in a subpopulation of dogs (N=10) analyzed by CBCT scan. On Day-90, CAL was reduced by 0.99mm compared to D0 (95% CI from -1.27 to -0.70 mm; n=60; p<0.0001). Likewise, the PPD was reduced by 0.98 mm (95% CI from -1.24 to -0.72 mm, n=60, p<0.0001).

Conclusion
This study supports VBX-1000 as a drug candidate to treat periodontal disease in dog. A randomized, placebo-controlled trial in dogs should confirm VBX-1000 potential in this indication.