R1 Therapeutics has announced that the first patient has been randomised in its global phase 2b trial of AP306, a first-in-class pan phosphate transporter inhibitor in development as a monotherapy for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis.
The multicentre, randomised, double-blind, placebo-controlled study is evaluating the safety, tolerability, and serum phosphate lowering effect of AP306 at fixed doses in patients receiving maintenance haemodialysis.
The study plans to enrol approximately 168 patients, randomised across six fixed-dose AP306 regimens and placebo, over an eight-week treatment period. The primary endpoint is the change in serum phosphate from baseline to the end of treatment, with secondary endpoints including the proportion of patients reaching the target phosphate range and the time to phosphate control. It is being conducted at multiple clinical sites across the USA and in China through R1’s global partnership with Alebund Pharmaceuticals
Hyperphosphatemia is one of the most common complications of advanced CKD and is almost universal in patients on dialysis. It is an independent risk factor for cardiovascular disease, bone disease, and mortality. Phosphate binders, the standard of care for 60 years, are limited by high pill burden and suboptimal gastrointestinal tolerance, contributing to poor adherence, R1 Therapeutics says in a press release.
“Randomising the first patient is a significant milestone for R1 and reflects the rapid pace at which our team and partners are moving,” said L Mary Smith, co-founder and chief operating officer of R1 Therapeutics. “We founded R1 to address a problem that has lacked therapeutic innovation for decades. Patients on dialysis face a heavy daily pill burden yet still struggle to keep their phosphate in range, and AP306 was designed to change that. Advancing it into phase 2b alongside our partner Alebund is a meaningful step forward, and we’re focused on generating the data needed to bring AP306 to patients.”
According to R1 Therapeutics, AP306 is the only agent that blocks the “active” transport of phosphate, targeting three key transporters in the gut, with the potential for rapid, effective phosphate lowering at a substantially reduced treatment burden. The phase 2b study builds on positive phase 2a data published in Kidney International Reports, which showed significant reductions in serum phosphate with good safety and tolerability. It is designed to expand the understanding of AP306’s activity and tolerability across a range of doses and dosing intervals, and to inform phase 3 development and regulatory discussions. Topline results are expected in the first half of 2027.
Glenn M Chertow (Stanford University School of Medicine, Palo Alto, USA), chair of R1’s scientific advisory board, added: “Hyperphosphatemia is among the most stubborn challenges we face in the day-to-day management of patients receiving maintenance dialysis, and is associated with mortality, cardiovascular events, and fracture. AP306 targets the absorption of phosphate through inhibition of three active transporters in the gut, providing a unique mechanism of action that could complement or potentially replace the use of commonly prescribed phosphate binders, agents that have been used for decades with only modest success. It is exciting to see this study begin, and I look forward to the insights it will provide on AP306’s potential to lower serum phosphate across a range of doses.”
AP306 was originally discovered by Chugai Pharmaceutical Co and subsequently licensed to Alebund Pharmaceuticals in 2021.
