twoXAR Pharmaceuticals, a drug discovery and development company focused on bringing first-in-class small molecules to market, today announced that two novel leads for the potential treatment of chronic kidney disease (CKD), TXR-1208 and TXR-1210, demonstrated significant efficacy and excellent tolerability in preclinical studies. TXR-1208 and TXR-1210 represent two different novel mechanisms of action (MOA). The overall timing to complete predictions, select hits and begin in vivo testing was a total of four weeks, significantly faster than traditional drug discovery processes. The data was presented at the 3rd Chronic Kidney Disease Drug Development (CKD3) Summit.
“A traditional R&D approach would have taken months or even years to identify just one potential target with a novel MOA,” stated Anjali Pandey, Ph.D. Senior Vice President of Nonclinical R&D and Chemistry at twoXAR. “But our unique approach simultaneously identified and selected two unexplored and promising candidates, TXR-1208 and TXR-1210, in just a few weeks. The favorable data presented today reaffirms our decision to advance a lead candidate as part of our CKD program.”
CKD is a slow and progressive loss of kidney function over several years, which can eventually cause permanent kidney failure. CKD often goes undetected and undiagnosed until the disease is well advanced, and the damage is irreversible resulting in poor survival rates. There are estimated to be 700 million cases of CKD worldwide.i Currently there is no cure for CKD.
“Chronic kidney disease is a silent condition that goes undiagnosed in the early stages, leaving patients with severe consequences, poor survival rates and in desperate need of new and innovative treatment options,” stated Michael J. Ross, MD, Chief, Division of Nephrology and Professor of Medicine and Development and Molecular Biology at Albert Einstein College of Medicine. “It’s encouraging to see positive pre-clinical data at this year’s CKD3 Summit, including research supporting novel mechanisms of action that have yet to be explored for the treatment of CKD.”
In vivo efficacy with TXR-1208 and TXR-1210 was evaluated using a unilateral ureteral obstruction (UUO) mouse model. Both TXR-1208 and TXR-1210 demonstrated significant decrease in kidney fibrosis and inflammation compared to TGFbeta mAb, the standard metric for positive efficacy. Both TXR-1208 and TXR-1210 also showed significant decreases in myofibroblast activation, significant decrease in infiltrating T cells and excellent tolerability by body weight.
twoXAR is committed to advancing TXR-1208 and TXR-1210 and is continuing to research both promising leads in pharmacokinetic, pharmacodynamic, and additional assays for kidney function and fibrosis/inflammation.
Chronic kidney disease (CKD) is a slow and progressive loss of kidney function over a period of several years, which can eventually cause permanent kidney failure. Since CKD often goes undetected and undiagnosed, damage is irreversible with only an estimated 35% of patients undergoing long-term dialysis having a 5-year survival rate.ii Currently, there is no cure for CKD and the current standard of care does not stop disease progression.
i Bikbov, B., Purcell, C., Levey, A., Smith, M., Abdoli, A., & Abebe, M. et al. (2020). Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet, 395(10225), 709-733. doi: 10.1016/s0140-6736(20)30045-3. 2017;23(47):8263-8276. doi:10.3748/wjg.v23.i47.8263
ii United States Renal Data System. 2018 Annual Data Report. Available at http://www.usrds.org/adr.aspx.
This article first appeared on PR Newswire.